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Sample records for caspase-3-positive bergmann glial

  1. Regional differences in the temporal expression of nonapoptotic caspase-3-positive Bergmann glial cells in the developing rat cerebellum

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    VelvetLee Finckbone

    2009-05-01

    Full Text Available Although caspases have been intimately linked to apoptotic events, some of the pro-apoptotic caspases also may regulate differentiation. We previously demonstrated that active caspase-3 is expressed and has an apparent non-apoptotic function during the development of cerebellar Bergmann glia. The current study seeks to further correlate active/cleaved caspase-3 expression with the developmental phenotype of Bergmann glia by examining regional differences in the temporal pattern of expression of cleaved caspase-3 immunoreactivity in lobules of the cerebellar vermis. In general, we found that the expression pattern of cleaved caspase-3 corresponds to the reported developmental temporal profile of the lobes and that its levels peak at 15 days and declines thereafter. Compared to intermediate or late maturing lobules, early maturing lobules had higher levels of active caspase-3 at earlier postnatal times. This period of postnatal development is precisely the time during which Bergmann glia initiate differentiation.

  2. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.

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    Guillem, Alain M; Martínez-Lozada, Zila; Hernández-Kelly, Luisa C; López-Bayghen, Esther; López-Bayghen, Bruno; Calleros, Oscar A; Campuzano, Marco R; Ortega, Arturo

    2015-11-01

    Glutamate, the main excitatory transmitter in the vertebrate brain, exerts its actions through the activation of specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of glutamate uptake systems, mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing an excessive glutamatergic stimulation and thus neuronal damage. Autism spectrum disorders comprise a group of syndromes characterized by impaired social interactions and anxiety. One or the most common drugs prescribed to treat these disorders is Methylphenidate, known to increase dopamine extracellular levels, although it is not clear if its sedative effects are related to a plausible regulation of the glutamatergic tone via the regulation of the glial glutamate uptake systems. To gain insight into this possibility, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity and protein levels of glutamate transporters was detected upon Methylphenidate exposure. Interestingly, this increase is the result of an augmentation of both the synthesis as well as the insertion of these protein complexes in the plasma membrane. These results favour the notion that glial cells are Methylphenidate targets, and that by these means could regulate dopamine turnover. PMID:26384974

  3. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

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    Chris I De Zeeuw

    2015-07-01

    Full Text Available Just as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One type of astrocyte, the Bergmann glial cell of the cerebellum, is a prime example of a highly diversified astrocyte type, the architecture of which is adapted to the cerebellar circuit and facilitates an impressive range of functions that optimize information processing in the adult brain. In this review we expand on the function of the Bergmann glial cell in the cerebellum to highlight the importance of astrocytes not only in housekeeping functions, but also in contributing to plasticity and information processing in the cerebellum.

  4. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

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    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  5. The inhibitory input to mouse cerebellar Purkinje cells is reciprocally modulated by Bergmann glial P2Y1 and AMPA receptor signaling.

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    Rudolph, Ramona; Jahn, Hannah M; Courjaret, Raphael; Messemer, Nanette; Kirchhoff, Frank; Deitmer, Joachim W

    2016-07-01

    Synaptic transmission has been shown to be modulated by glial functions, but the modes of specific glial action may vary in different neural circuits. We have tested the hypothesis, if Bergmann GLIA (BG) are involved in shaping neuronal communication in the mouse cerebellar cortex, using acutely isolated cerebellar slices of wild-type (WT) and of glia-specific receptor knockout mice. Activation of P2Y1 receptors by ADP (100 µM) or glutamatergic receptors by AMPA (0.3 µM) resulted in a robust, reversible and repeatable rise of evoked inhibitory input in Purkinje cells by 80% and 150%, respectively. The ADP-induced response was suppressed by prior application of AMPA, and the AMPA-induced response was suppressed by prior application of ADP. Genetic deletion or pharmacological blockade of either receptor restored the response to the other receptor agonist. Both ADP and AMPA responses were sensitive to Rose Bengal, which blocks vesicular glutamate uptake, and to the NMDA receptor antagonist D-AP5. Our results provide strong evidence that activation of both ADP and AMPA receptors, located on BGs, results in the release of glutamate, which in turn activates inhibitory interneurons via NMDA-type glutamate receptors. This infers that BG cells, by means of metabotropic signaling via their AMPA and P2Y1 receptors, which mutually suppress each other, would interdependently contribute to the fine-tuning of Purkinje cell activity in the cerebellar cortex. GLIA 2016. GLIA 2016;64:1265-1280. PMID:27144942

  6. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

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    Aarti eNagayach

    2014-10-01

    Full Text Available Behavioural impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45mg/ kg body weight; intraperitoneally. Motor function alterations were studied using Rotarod test (motor coordination and grip strength (muscle activity at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Scenario of glial (astroglia and microglia activation, cell death and glutamate transportation was gauged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labelling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioural alterations following STZ-induced diabetes.

  7. Martin Bergmann: The Last 21 Years.

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    Feiner, Kenneth

    2015-06-01

    Martin Bergmann has contributed to our understanding of psychoanalysis for more than sixty years. A review of his contributions to psychoanalysis was completed in 1994, when Bergmann was 83 years old. Consideration of his remarkable productivity in the last twenty years clearly demonstrates the need to update this review. In these years, he extended his writing on the history of psychoanalysis, added to his contributions to an understanding of love, advanced ideas about psychoanalytic technique, and wrote two books on Shakespeare, as well as doing work in anthropology, sociology, literature, history, and religious studies. This paper reviews that work. PMID:26080097

  8. The cylindrical condition and Einstein-Bergmann theory

    International Nuclear Information System (INIS)

    Recently work on unification of forces has centered on constructing higher-dimensional theories. Typically a higher-dimensional space is a direct product of a four-dimensional space with a compact space that has a high degree of symmetry. The idea of compactification was first proposed by Klein and later mathematically formalized by Einstein and Bergmann. The origin of compactification is based on the cylindrical condition proposed by Kaluza as a practical approximation. The cylindrical condition was used as an assumption by Klein. Later, based on some geometrical assumptions, the cylindrical condition was mathematically derived by Einstein and Bergmann. Kaluza's aim was undoubtedly to obtain some new physical aspect of gravitation and electricity by introducing a unitary field structure. It is shown that the Einstein-Bergmann theory implies that a rigorous cylindrical condition may not be compatible with Kaluza's theory

  9. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

    NARCIS (Netherlands)

    C.I. de Zeeuw (Chris); T.M. Hoogland (Tycho)

    2015-01-01

    textabstractJust as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One

  10. Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells.

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    Flores-Méndez, Marco; Ramírez, Diana; Alamillo, Nely; Hernández-Kelly, Luisa C; Del Razo, Luz María; Ortega, Arturo

    2014-08-17

    Fluoride is an environmental pollutant present in dental products, food, pesticides and water. The latter, is the greatest source of exposure to this contaminant. Structural and functional damages to the central nervous system are present in exposed population. An established consequence of the neuronal is the release of a substantial amount of glutamate to the extracellular space, leading to an excitotoxic insult. Glutamate exerts its actions through the activation of specific plasma membrane receptors and transporters present in neurons and in glia cells and it is the over-activation of glutamate receptors and transporters, the biochemical hallmark of neuronal and oligodendrocyte cell death. In this context, taking into consideration that fluoride leads to degeneration of cerebellar cells, we took the advantage of the well-established model of cerebellar Bergmann glia cultures to gain insight into the molecular mechanisms inherent to fluoride neurotoxicity that might be triggered in glia cells. We could establish that fluoride decreases [(35)S]-methionine incorporation into newly synthesized polypeptides, in a time-dependent manner, and that this halt in protein synthesis is the result of a decrease in the elongation phase of translation, mediated by an augmentation of eukaryotic elongation factor 2 phosphorylation. These results favor the notion of glial cells as targets of fluoride toxicity and strengthen the idea of a critical involvement of glia cells in the function and dysfunction of the brain. PMID:24954634

  11. Preferential Transport and Metabolism of Glucose in Bergmann Glia over Purkinje Cells: A Multiphoton Study of Cerebellar Slices

    Institute of Scientific and Technical Information of China (English)

    L.F.BARROS; R.COURJARET; P.JAKOBY; A.LOAIZA; C.LOHR; J.W.DEITMER

    2009-01-01

    了解不同类型的细胞如何处理葡萄糖有助于解释能量供应是如何是如何根据大脑能量需求来进行调整的.荧光追踪结合共聚焦显微镜技术已用于研究培养的脑细胞摄取葡萄糖的实时动态过程.本文采用这种技术利用多光子显微镜观察急性制备的大鼠小脑脑片.带荧光的葡萄糖类似物2NBDG和6NBDG在小脑皮质的分子层中的转运速度比其在蒲肯野细胞胞体和颗粒细胞中快若干倍.洗脱游离示踪剂后,可见大部分磷酸化示踪剂都位于Bergmann胶质细胞,用胶质细胞标记物sulforhodamine 101免疫染色后进一步确认这一结果.有效回收荧光光漂白后显示,2NBDG-P可通过Bergmann胶质细胞之间的缝隙连接沿着分子层水平扩散.本文的结果表明在急性小脑切片中,Bergmann胶质细胞对葡萄糖的转运能力和糖酵解率高于蒲肯野细胞若干倍.由于小脑主要由葡萄糖提供能量,蒲肯野神经元被认为比Bergmann胶质细胞更耗能量,这些结果表明,在胶质细胞和神经元之间存在类似乳酸的能量代谢物介导的环路.%Knowing how different cell types handle glucose should help to decipher how energy supply is adjusted to energy demand in the brain. Previously, the uptake of glucose by cultured brain cells was studied in real-time using fluorescent tracers and confocal microscopy. Here, we have adapted this technique to acute slices prepared from the rat cerebellum by means of multiphoton microscopy. The transport of the fluorescent glucose analogs 2NBDG and 6NBDG was several-fold faster in the molecular layer of the cerebellar cortex than in Purkinje cell somata and granule cells. After washout of free tracer, it became apparent that most phosphorylated tracer was located in Bergmann glia, which was confirmed by counterstaining with the glial marker sulforhodamine 101. The effective recovery of fluorescence after photobleaching showed that 2NBDG-P can diffuse

  12. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

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    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

  13. The cold-water connection: Bergmann's rule in North American freshwater fishes.

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    Rypel, Andrew L

    2014-01-01

    Understanding general rules governing macroecological body size variations is one of the oldest pursuits in ecology. However, this science has been dominated by studies of terrestrial vertebrates, spurring debate over the validity of such rules in other taxonomic groups. Here, relationships between maximum body size and latitude, temperature, and elevation were evaluated for 29 North American freshwater fish species. Bergmann's rule (i.e., that body size correlates positively with latitude and negatively with temperature) was observed in 38% of species, converse Bergmann's rule (that body size correlates negatively with latitude and positively with temperature) was observed in 34% of species, and 28% of species showed no macroecological body size relationships. Most notably, every species that expressed Bergmann's rule was a cool- or cold-water species while every species that expressed converse Bergmann's rule was a warm-water species, highlighting how these patterns are likely connected to species thermal niches. This study contradicts previous research suggesting Bergmann's rule does not apply to freshwater fishes, and is congruent with an emerging paradigm of variable macroecological body size patterns in poikilotherms. PMID:24334744

  14. Adherence to Bergmann's rule by lizards may depend on thermoregulatory mode: support from a nocturnal gecko.

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    Penniket, Sophie; Cree, Alison

    2015-06-01

    Bergmann's rule predicts an increase in body size with decreasing environmental temperature; however, the converse pattern has been found in the majority of lizards studied to date. For these ectotherms, small body size may provide thermal benefits (rapid heat uptake when basking), which would be highly advantageous in cold environments. Yet such an advantage may not exist in nocturnal lizards (which do not avidly bask), in which Bergmann's rule has not been closely studied. We have examined whether the body size of a primarily nocturnal gecko, Woodworthia "Otago/Southland" changed with elevation and operative temperature (determined using physical copper models). In a laboratory study, we investigated whether thermoregulatory mode (heliothermy or thigmothermy) alters the effect of body size on heating and cooling rates. This gecko followed Bergmann's rule, thereby showing the opposite of the dominant pattern in diurnal lizards. Size at maturity, maximum size of adults and size at birth were larger at higher elevations and at lower operative temperatures. Using physical models, we found that large body size can confer thermal benefits for nocturnal lizards that remain within diurnal retreats. Bergmann's rule should not be dismissed for all lizards. Our results clearly support Bergmann's rule for at least one thigmothermic species, for which large body size may provide thermal benefits. Future studies on Bergmann's rule in lizards should consider thermoregulatory mode. We advocate that this ecogeographic rule be examined in relation to operative temperature measured at field sites. Finally, we predict that climate warming may weaken the relationship between body size and elevation in this gecko. PMID:25663371

  15. Bergmann's rule near the equator: latitudinal clines in body size of an Andean passerine bird.

    OpenAIRE

    Graves, G R

    1991-01-01

    Critical correlative support for Bergmann's ecogeographic rule is provided by symmetrical patterns of size variation in Diglossa carbonaria, a tropical passerine bird whose geographic range in the Andes Mountains of South America straddles the equator. Body size is positively correlated with latitude both north and south of the equator. Moreover, parapatric taxa that exhibit either partial (north-western Bolivia) or complete (northern Peru) reproductive isolation converge in body size. Relati...

  16. The evolution of body size under environmental gradients in ectotherms: why should Bergmann's rule apply to lizards?

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    Tregenza Tom

    2008-02-01

    Full Text Available Abstract Background The impact of environmental gradients on the evolution of life history traits is a central issue in macroecology and evolutionary biology. A number of hypotheses have been formulated to explain factors shaping patterns of variation in animal mass. One such example is Bergmann's rule, which predicts that body size will be positively correlated with latitude and elevation, and hence, with decreasing environmental temperatures. A generally accepted explanation for this phenotypic response is that as body mass increases, body surface area gets proportionally smaller, which contributes to reduced rates of heat-loss. Phylogenetic and non-phylogenetic evidence reveals that endotherms follow Bergmann's rule. In contrast, while previous non-phylogenetic studies supported this prediction in up to 75% of ectotherms, recent phylogenetic comparative analyses suggest that its validity for these organisms is controversial and less understood. Moreover, little attention has been paid to why some ectotherms conform to this rule, while others do not. Here, we investigate Bergmann's rule in the six main clades forming the Liolaemus genus, one of the largest and most environmentally diverse genera of terrestrial vertebrates. A recent study conducted on some species belonging to four of these six clades concluded that Liolaemus species follow Bergmann's rule, representing the only known phylogenetic support for this model in lizards. However, a later reassessment of this evidence, performed on one of the four analysed clades, produced contrasting conclusions. Results Our results fail to support Bergmann's rule in Liolaemus lizards. Non-phylogenetic and phylogenetic analyses showed that none of the studied clades experience increasing body size with increasing latitude and elevation. Conclusion Most physiological and behavioural processes in ectotherms depend directly upon their body temperature. In cold environments, adaptations to gain heat

  17. Functional modeling of neural-glial interaction

    DEFF Research Database (Denmark)

    Postnov, D.E.; Ryazanova, L.S.; Sosnovtseva, Olga

    2007-01-01

    We propose a generalized mathematical model for a small neural-glial ensemble. The model incorporates subunits of the tripartite synapse that includes a presynaptic neuron, the synaptic terminal itself, a postsynaptic neuron, and a glial cell. The glial cell is assumed to be activated via two dif...

  18. Do glial cells control pain?

    OpenAIRE

    Suter, Marc R; Wen, Yeong-Ray; Decosterd, Isabelle; Ji, Ru-Rong

    2007-01-01

    Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer’s and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not onl...

  19. Elastic constants of plastic crystals by Schaefer-Bergmann scattering: crystalline cyclohexane and deuteromethane

    International Nuclear Information System (INIS)

    The Schaefer-Bergmann technique for sound velocity measurement has been adapted for use with solidified liquids and gases. The advantages of this method for measuring elastic constants of plastic crystals are discussed. A method for determining both the elastic constants and the spacial orientation of the crystal from the light scattering data is presented. Measurements of sound velocity at 10 MHz in both liquid and solid tetradeuteromethane (CD4) and cyclohexane (C6H12) are described. The elastic constants of CD4 at 85.57 K are found to be C11 = 2.056 +- .015, C12 = 1.542 +- .015, C44 = 0.9387 +- .005 GPa. For cyclohexane at 278.6 K the results of the measurements are C11 = 2.5795 +- .015, C12 + 2C44 = 2.967 +- .03 GPa. It is argued that the separate elastic constants of cyclohexane are C12 = 2.251, C44 = 0.358 GPa. The presence of dispersion in the case of cyclohexane and its absence in the case of methane is noted. Some pecularities in the elastic behavior of plastic crystals are discussed in the light of an expected coupling between translational and orientational excitations in the crystal

  20. Bergmann's rule is maintained during a rapid range expansion in a damselfly.

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    Hassall, Christopher; Keat, Simon; Thompson, David J; Watts, Phillip C

    2014-02-01

    Climate-induced range shifts result in the movement of a sample of genotypes from source populations to new regions. The phenotypic consequences of those shifts depend upon the sample characteristics of the dispersive genotypes, which may act to either constrain or promote phenotypic divergence, and the degree to which plasticity influences the genotype-environment interaction. We sampled populations of the damselfly Erythromma viridulum from northern Europe to quantify the phenotypic (latitude-body size relationship based on seven morphological traits) and genetic (variation at microsatellite loci) patterns that occur during a range expansion itself. We find a weak spatial genetic structure that is indicative of high gene flow during a rapid range expansion. Despite the potentially homogenizing effect of high gene flow, however, there is extensive phenotypic variation among samples along the invasion route that manifests as a strong, positive correlation between latitude and body size consistent with Bergmann's rule. This positive correlation cannot be explained by variation in the length of larval development (voltinism). While the adaptive significance of latitudinal variation in body size remains obscure, geographical patterns in body size in odonates are apparently underpinned by phenotypic plasticity and this permits a response to one or more environmental correlates of latitude during a range expansion. PMID:23913531

  1. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  2. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...... repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic...... nerve, however, only the Na(+)/K(+)-ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance. The glial cell swelling associated with K(+) clearance is prevented under conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The Na(+)/K(+)/Cl(-) cotransporter is...

  3. Glial heterotopia of the oral cavity

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    Radhames E. Lizardo

    2015-07-01

    Full Text Available We report an unusual case of a glial heterotopia arising from the oral cavity of an African neonate. The patient presented with an external pedunculated oral mass which was connected to the anterior hard palate by a firm, rubbery stalk of mucosal tissue. While the mass appeared painless, it interfered with the infant's feeding and was disturbing to the parents. After a computed tomography scan excluded an intracranial connection, the mass was excised at its base and sent for biopsy. Histopathology examination confirmed glial heterotopia. Glial heterotopias should be included in the differential diagnosis of congenital masses in the oral region.

  4. Glial Contributions to Neural Function and Disease.

    Science.gov (United States)

    Rasband, Matthew N

    2016-02-01

    The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have unique protein compositions that reflect their diverse functions, and these compositions can change depending on activity or disease. Here, I discuss the major classes and functions of glial cells in the central and peripheral nervous systems. I describe proteomic approaches that have been used to investigate glial cell function and composition and the experimental limitations faced by investigators working with glia. PMID:26342039

  5. Glial cells are involved in itch processing

    DEFF Research Database (Denmark)

    Andersen, Hjalte H.; Arendt-Nielsen, Lars; Gazerani, Parisa

    2016-01-01

    development of chronic itch akin to their more investigated role in chronic pain. Improvements are needed in the management of chronic itch, and future basic and interventional studies on glial activity modulation would both enhance our understanding of mechanisms underlying the chronification of itch and...... provide novel opportunities for the future prevention or treatment of this debilitating and common condition....

  6. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

    OpenAIRE

    Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R

    2012-01-01

    Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Drape...

  7. Dichroplus vittatus (Orthoptera: Acrididae) follows the converse to Bergmann's rule although male morphological variability increases with latitude.

    Science.gov (United States)

    Bidau, C J; Martí, D A

    2007-02-01

    Geographic body size variation was analysed in males and females of 19 populations of the South American grasshopper Dichroplus vittatus Bruner spanning 20 degrees of latitude and 2700 m of altitude. Using mean and maximum body length of each sex and factors obtained from principal components analyses of six morphometric linear characters it was shown that D. vittatus followed the converse to Bergmann's rule latitudinally but not altitudinally where no significant trends were observed. For males, variability of body size increased with latitude but not with altitude. Both types of trends were significantly correlated with mean annual temperature and minimum annual temperature (positive correlations), and two estimators of seasonality, the coefficients of variation of mean annual temperature (negative) and mean annual precipitation (positive). Some allometric relationships also showed geographic variation. It is suggested that the observed decrease in size with latitude together with the increase in morphological variability is a consequence of a number of factors: the shortening of the growing season southwards; the increasing seasonality and climatic unpredictability; and the fact that the species exhibits protandry which contributes to smaller and more variable size in males and smaller but more constant body size in females. PMID:17298684

  8. Progress in glial cell studies in some laboratories in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Glial cells in the central nervous system(CNS) consist of a heterogeneous population of cell types,each characterized by distinct morphological features,physiological properties,and specific markers.In contrast to the previous view that glial cells were passive elements in the brain,accumulating evidence suggests that glial cells are active participants in various brain functions and brain disorders.This review summarizes recent progress of glial cell studies from several groups in China,ranging from studies about the mechanisms of neuron-glia crosstalking to investigations on the roles of glial cells in various CNS disorders.

  9. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

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    Gilmore, S.A.; Sims, T.J. [Arkansas Univ., Little Rock, AR (United States). Medical Center

    1997-01-01

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author).

  10. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

    International Nuclear Information System (INIS)

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author)

  11. Glial heterotopia of the oral cavity

    OpenAIRE

    Lizardo, Radhames E.; Simone Langness; Hassan Mumun; James Murphy; Robert Newbury; Patricia Bromberger; Bickler, Stephen W.

    2015-01-01

    We report an unusual case of a glial heterotopia arising from the oral cavity of an African neonate. The patient presented with an external pedunculated oral mass which was connected to the anterior hard palate by a firm, rubbery stalk of mucosal tissue. While the mass appeared painless, it interfered with the infant's feeding and was disturbing to the parents. After a computed tomography scan excluded an intracranial connection, the mass was excised at its base and sent for biopsy. Histopath...

  12. Complete elastic constants of α−BaB{sub 2}O{sub 4}: Resonant ultrasound spectroscopy versus Schaefer-Bergmann diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Pfeiffer, Jonathan B.; Kaufman, Yaniv; Wagner, Kelvin H. [Dept. of Electrical and Computer Engineering, University of Colorado, Boulder, CO (United States); Ledbetter, Hassel [Dept. of Mechanical Engineering, University of Colorado, Boulder, CO (United States)

    2014-05-27

    We utilized both resonant ultrasound spectroscopy (RUS) and Schaefer-Bergmann diffraction patterns (SBDP) to measure the elastic stiffness coefficients of the trigonal, non-piezo-electric crystal α−BaB{sub 2}O{sub 4}. RUS determines the elastic coefficients of a sample by matching measured resonant frequencies to a model of resonances. SBDP deduces the elastic coefficients by fitting the measured shape of the acousto-optic diffraction pattern to an acoustic slowness surface cross-section. We present our measured elastic coefficients of α−BaB{sub 2}O{sub 4} from both RUS and SBDP experiments.

  13. Glial origin of rapidly adhering amniotic fluid cells.

    OpenAIRE

    Aula, P; von Koskull, H; Teramo, K; Karjalainen, O; Virtanen, I.; Lehto, V P; Dahl, D

    1980-01-01

    Rapidly adhering cells (RA cells) from the amniotic fluid of a pregnancy with fetal anencephaly were investigated by immunofluorescence assay with an antiserum against glial cells. After 24 hours' cultivation a high proportion of the cells showed positive glial-specific fluorescence, whereas no staining was seen in cells from samples of normal amniotic fluid. At the 24th week the mother was delivered of a stillborn infant with anencephaly. Immunofluorescence staining of RA cells with glial-sp...

  14. Electrical Coupling Between Glial Cells in the Rat Retina

    OpenAIRE

    Ceelen, Paul W.; Lockridge, Amber; Newman, Eric A.

    2001-01-01

    The strength of electrical coupling between retinal glial cells was quantified with simultaneous whole-cell current-clamp recordings from astrocyte–astrocyte, astrocyte–Müller cell, and Müller cell–Müller cell pairs in the acutely isolated rat retina. Experimental results were fit and space constants determined using a resistive model of the glial cell network that assumed a homogeneous two-dimensional glial syncytium. The effective space constant (the distance from the point of stimulation t...

  15. Enteric glial cells have specific immunosuppressive properties.

    Science.gov (United States)

    Kermarrec, Laetitia; Durand, Tony; Neunlist, Michel; Naveilhan, Philippe; Neveu, Isabelle

    2016-06-15

    Enteric glial cells (EGC) have trophic and neuroregulatory functions in the enteric nervous system, but whether they exert a direct effect on immune cells is unknown. Here, we used co-cultures to show that human EGC can inhibit the proliferation of activated T lymphocytes. Interestingly, EGC from Crohn's patients were effective at one EGC for two T cells whereas EGC from control patients required a ratio of 1:1. These data suggest that EGC contribute to local immune homeostasis in the gastrointestinal wall. They also raise the possibility that EGC have particular immunosuppressive properties in inflammatory bowel diseases such as Crohn's disease. PMID:27235353

  16. Tumores intraventriculares supratentoriales de origen glial

    OpenAIRE

    Miguel A Esquivel M; Jose A Quesada G; Desireé Gutierrez G

    2015-01-01

    Los tumores gliales intraventriculares representan un gran reto de acceso neuroquirúrgico debido a su localización profunda, asociación intima con numerosas estructuras vasculares de áreas críticas cerebrales y su relación circunferencial a múltiples tractos subcorticales. Debido a todo esto, el acceso quirúrgico a estas regiones, debe incluir una serie de consideraciones minuciosas anatómicas para minimizar el riesgo de lesión a estructuras de considerable importancia y funcionabilidad y log...

  17. Glial cells as drug targets: What does it take?

    Science.gov (United States)

    Möller, Thomas; Boddeke, Hendrikus W G M

    2016-10-01

    The last two decades have brought a significant increase in our understanding of glial biology and glial contribution to CNS disease. Yet, despite the fact that glial cells make up the majority of CNS cells, no drug specifically targeting glial cells is on the market. Given the long development times of CNS drugs, on average over 12 years, this is not completely surprising. However, there is increasing interest from academia and industry to exploit glial targets to develop drugs for the benefit of patients with currently limited or no therapeutic options. CNS drug development has a high attrition rate and has encountered many challenges. It seems unlikely that developing drugs against glial targets would be any less demanding. However, the knowledge generated in traditional CNS drug discovery teaches valuable lessons, which could enable the glial community to accelerate the cycle time from basic discovery to drug development. In this review we will discuss steps necessary to bring a "glial target idea" to a clinical development program. GLIA 2016;64:1742-1754. PMID:27121701

  18. Glial heterotopia of the lip: A rare presentation

    Directory of Open Access Journals (Sweden)

    Mehmet Dadaci

    2016-01-01

    Full Text Available Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery.

  19. Tumores intraventriculares supratentoriales de origen glial

    Directory of Open Access Journals (Sweden)

    Miguel A Esquivel M

    2015-12-01

    Full Text Available Los tumores gliales intraventriculares representan un gran reto de acceso neuroquirúrgico debido a su localización profunda, asociación intima con numerosas estructuras vasculares de áreas críticas cerebrales y su relación circunferencial a múltiples tractos subcorticales. Debido a todo esto, el acceso quirúrgico a estas regiones, debe incluir una serie de consideraciones minuciosas anatómicas para minimizar el riesgo de lesión a estructuras de considerable importancia y funcionabilidad y lograr una resección máxima posible. Presentamos una reseña de 4 casos los cuales fueron ingresados y atendidos por el servicio de neurocirugía del Hospital México, los cuales ingresaron en un intervalo de 8 meses entre agosto del 2012 y febrero del 2013.

  20. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our...... ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for...... studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  1. Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies

    OpenAIRE

    Karsten Mueller; Blasig, Ingolf E.; Johann Steiner; Hashim Abdul-Khaliq; Julia Sacher; Matthias L. Schroeter

    2010-01-01

    It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive tha...

  2. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K;

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated by...

  3. Neuroimaging Biomarkers for Epilepsy: Advances and Relevance to Glial Cells

    OpenAIRE

    Obenaus, Andre

    2013-01-01

    Glial cells play an important role in normal brain function and emerging evidence would suggest that their dysfunction may be responsible for some epileptic disease states. Neuroimaging of glial cells is desirable, but there are no clear methods to assess neither their function nor localization. Magnetic resonance imaging (MRI) is now part of a standardized epilepsy imaging protocol to assess patients. Structural volumetric and T2-weighted imaging changes can assist in making a positive diagn...

  4. Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Viktor Kis

    Full Text Available Lipid droplets (LDs are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain's LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp, as we have demonstrated through light- and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain.

  5. Porovnání dopravních systémů Bergmann a Annaburger v podnicích zemědělské prvovýroby.

    OpenAIRE

    HAVLÍK, Josef

    2011-01-01

    This thesis compares two tractor traffic exchange systems, Bergmann and Annaburger, in two companies of basic agriculture industry. Tractor traffic systems are composed of towing and exchange vehicle which can be a carrier of several types of vehicle body. Bed, spreader and cistern are concerned in this case. Engineering chracteristics and operational experiences of every single exchange system were compared. Futher functionality, time demandingness of body exchange, machine operating comfort...

  6. Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

    Directory of Open Access Journals (Sweden)

    Shen Yujun

    2012-11-01

    Full Text Available Abstract Background Mesencephalic astrocyte-derived neurotrophic factor (MANF, a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins. Results We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

  7. Distinctive glial and neuronal interfacing on nanocrystalline diamond.

    Directory of Open Access Journals (Sweden)

    Amel Bendali

    Full Text Available Direct electrode/neuron interfacing is a key challenge to achieve high resolution of neuronal stimulation required for visual prostheses. Neuronal interfacing on biomaterials commonly requires the presence of glial cells and/or protein coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with a remarkably large potential window for the electrical stimulation of tissues. Using adult retinal cell cultures from rats, we found that glial cells and retinal neurons grew equally well on glass and nanocrystalline diamond. The use of a protein coating increased cell survival, particularly for glial cells. However, bipolar neurons appeared to grow even in direct contact with bare diamond. We investigated whether the presence of glial cells contributed to this direct neuron/diamond interface, by using purified adult retinal ganglion cells to seed diamond and glass surfaces with and without protein coatings. Surprisingly, these fully differentiated spiking neurons survived better on nanocrystalline diamond without any protein coating. This greater survival was indicated by larger cell numbers and the presence of longer neurites. When a protein pattern was drawn on diamond, neurons did not grow preferentially on the coated area, by contrast to their behavior on a patterned glass. This study highlights the interesting biocompatibility properties of nanocrystalline diamond, allowing direct neuronal interfacing, whereas a protein coating was required for glial cell growth.

  8. Axon-glial interactions in the central nervous system

    OpenAIRE

    Butt, Arthur; Bay, Virginia

    2011-01-01

    Axon-glial interactions are critical for brain information transmission and processing. In the CNS, this is a function of the major types of glia – astrocytes, oligodendrocytes and novel NG2-glia. This special issue of the Journal of Anatomy comprises contributions arising from a symposium entitled ‘Axon-glial interactions in the CNS’, held at the University of Portsmouth, UK in July 2010. The aim of the special issue is to bring together an international group of experts to demonstrate the c...

  9. C/EBPs en la activación glial

    OpenAIRE

    Ejarque-Ortiz, Aroa

    2008-01-01

    [spa] La activación glial es un proceso que se ha implicado en diversas patologías entre las que se incluyen diferentes enfermedades neurodegenerativas, como la enfermedad de Alzheimer o la Esclerosis Lateral Amiotrófica. Esto se debe a que durante la activación glial se producen mediadores proinflamatorios, como la ciclooxigenasa (COX-2), el óxido nítrico (NO), factor de necrosis tumoral (TNF-alfa), la interleuquina-1 (IL-1) o la interleuquina-6 (IL-6), que presentan un potencial neurotóxico...

  10. Rapid method for culturing embryonic neuron-glial cell cocultures

    DEFF Research Database (Denmark)

    Svenningsen, Åsa Fex; Shan, Wei-Song; Colman, David R;

    2003-01-01

    enteric neurons is seen after 3 weeks (2 weeks in ascorbic acid), suggesting that basal lamina production is important even for glial ensheathment in the enteric nervous system. No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous...

  11. Depression as a Glial-Based Synaptic Dysfunction

    OpenAIRE

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M.; Gonçalves, Francisco Q.; Real, Joana I.; Prediger, Rui D.; Gonçalves, Nélio; Gomes, Catarina A.; Canas, Paula M.; Agostinho, Paula; Cunha, Rodrigo A.

    2016-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes...

  12. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N.; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer’s disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression

  13. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Nofar Torika

    Full Text Available The circulating renin-angiotensin system (RAS, including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker on tumor necrosis factor-α (TNF-α, interleukin 1-β (IL1-β and nitric oxide (NO release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor. Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the

  14. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression of

  15. Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

    OpenAIRE

    He Zhang; Ya-jing Su; Wei-wei Zhou; Shao-wei Wang; Peng-xin Xu; Xiao-lin Yu; Rui-tian Liu

    2014-01-01

    Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide...

  16. Glial cell development and function in the Drosophila visual system

    OpenAIRE

    CHOTARD, CAROLE; Salecker, Iris

    2007-01-01

    In the developing nervous system, building a functional neuronal network relies on coordinating the formation, specification and survival to diverse neuronal and glial cell subtypes. The establishment of neuronal connections further depends on sequential neuron–neuron and neuron–glia interactions that regulate cell-migration patterns and axon guidance. The visual system of Drosophila has a highly regular, retinotopic organization into reiterated interconnected synaptic circuits. It is therefo...

  17. Brain Connexins in Demyelinating Diseases: Therapeutic Potential of Glial Targets

    OpenAIRE

    Cotrina, Maria Luisa; Nedergaard, Maiken

    2012-01-01

    Several demyelinating syndromes have been linked to mutations in glial gap junction proteins, the connexins. Although mutations in connexins of the myelinating cells, Schwann cells and oligodendrocytes, were initially described, recent data have shown that astrocytes also play a major role in the demyelination process. Alterations in astrocytic proteins directly affect the oligodendrocytes’ ability to maintain myelin structure, and associated astrocytic proteins that regulate water and ionic ...

  18. JC polyomavirus in the aetiology and pathophysiology of glial tumours.

    Science.gov (United States)

    Eftimov, Tihomir; Enchev, Yavor; Tsekov, Iliya; Simeonov, Plamen; Kalvatchev, Zlatko; Encheva, Elitsa

    2016-01-01

    Glial brain tumours with their poor prognosis, limited treatment modalities and unclear detailed pathophysiology represent a significant health concern. The purpose of the current study was to investigate and describe the possible role of the human polyomavirus JC as an underlying cancerogenic or co-cancerogenic factor in the complex processes of glial tumour induction and development. Samples from 101 patients with glial tumours were obtained during neurosurgical tumour resection. Small tissue pieces were taken from several areas of the histologically verified solid tumour core. Biopsies were used for DNA extraction and subsequent amplification reactions of sequences from the JC viral genome. Real-time polymerase chain reaction was used for detection and quantification of its non-coding control region (NCCR) and gene encoding the regulatory protein Large T antigen (LT). An average of 37.6% of all patients was found to be LT positive, whereas only 6.9% tested positive for NCCR. The analysis of the results demonstrated significant variance between the determined LT prevalence and the rate for NCCR, with a low starting copy number in all positive samples and threshold cycles in the range of 36 to 42 representing viral load in the range from 10 to 1000 copies/μl. The results most probably indicate incomplete JC viral replication. Under such conditions, mutations in the host cell genome may be accumulated due to interference of the virus with the host cell machinery, and eventually malignant transformation may occur. PMID:26560882

  19. Glial biomarkers in human central nervous system disease.

    Science.gov (United States)

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. PMID:27228454

  20. Dynamical mean field model of a neural-glial mass.

    Science.gov (United States)

    Sotero, Roberto C; Martínez-Cancino, Ramón

    2010-04-01

    Our goal is to model the behavior of an ensemble of interacting neurons and astrocytes (the neural-glial mass). For this, a model describing N tripartite synapses is proposed. Each tripartite synapse consists of presynaptic and postsynaptic nerve terminals, as well as the synaptically associated astrocytic microdomain, and is described by a system of 13 stochastic differential equations. Then, by applying the dynamical mean field approximation (DMA) (Hasegawa, 2003a , 2003b ) the system of 13N equations is reduced to 13(13 + 2) = 195 deterministic differential equations for the means and the second-order moments of local and global variables. Simulations are carried out for studying the response of the neural-glial mass to external inputs applied to either the presynaptic terminals or the astrocytes. Three cases were considered: the astrocytes influence only the presynaptic terminal, only the postsynaptic terminal, or both the presynaptic and postsynaptic terminals. As a result, a wide range of responses varying from singles spikes to train of spikes was evoked on presynaptic and postsynaptic terminals. The experimentally observed phenomenon of spontaneous activity in astrocytes was replicated on the neural-glial mass. The model predicts that astrocytes can have a strong and activity-dependent influence on synaptic transmission. Finally, simulations show that the dynamics of astrocytes influences the synchronization ratio between neurons, predicting a peak in the synchronization for specific values of the astrocytes' parameters. PMID:20028223

  1. Radial glial cell transformation to astrocytes is bidirectional: regulation by a diffusible factor in embryonic forebrain.

    OpenAIRE

    Hunter, K E; Hatten, M E

    1995-01-01

    During development of mammalian cerebral cortex, two classes of glial cells are thought to underlie the establishment of cell patterning. In the embryonic period, migration of young neurons is supported by a system of radial glial cells spanning the thickness of the cortical wall. In the neonatal period, neuronal function is assisted by the physiological support of a second class of astroglial cell, the astrocyte. Here, we show that expression of embryonic radial glial identity requires extri...

  2. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  3. Guanosine protects glial cells against 6-hydroxydopamine toxicity.

    Science.gov (United States)

    Giuliani, Patricia; Ballerini, Patrizia; Buccella, Silvana; Ciccarelli, Renata; Rathbone, Michel P; Romano, Silvia; D'Alimonte, Iolanda; Caciagli, Francesco; Di Iorio, Patrizia; Pokorski, Mieczyslaw

    2015-01-01

    Increasing body of evidence indicates that neuron-neuroglia interaction may play a key role in determining the progression of neurodegenerative diseases including Parkinson's disease (PD), a chronic pathological condition characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra. We have previously reported that guanosine (GUO) antagonizes MPP(+)-induced cytotoxicity in neuroblastoma cells and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA) and beta-amyloid-induced apoptosis of SH-SY5Y cells. In the present study we demonstrate that GUO protected C6 glioma cells, taken as a model system for astrocytes, from 6-OHDA-induced neurotoxicity. We show that GUO, either alone or in combination with 6-OHDA activated the cell survival pathways ERK and PI3K/Akt. The involvement of these signaling systems in the mechanism of the nucleoside action was strengthened by a reduction of the protective effect when glial cells were pretreated with U0126 or LY294002, the specific inhibitors of MEK1/2 and PI3K, respectively. Since the protective effect on glial cell death of GUO was not affected by pretreatment with a cocktail of nucleoside transporter blockers, GUO transport and its intracellular accumulation were not at play in our in vitro model of PD. This fits well with our data which pointed to the presence of specific binding sites for GUO on rat brain membranes. On the whole, the results described in the present study, along with our recent evidence showing that GUO when administered to rats via intraperitoneal injection is able to reach the brain and with previous data indicating that it stimulates the release of neurotrophic factors, suggest that GUO, a natural compound, by acting at the glial level could be a promising agent to be tested against neurodegeneration. PMID:25310956

  4. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda;

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways of the...... establishing the positive feedback in glutamate release that is critical for the self-sustained activity of the postsynaptic neuron. This mechanism differs from the mechanisms of the astrocyte-neuron signaling previously reported....

  5. Diffusion tensor magnetic resonance imaging of glial brain tumors

    International Nuclear Information System (INIS)

    Aim: To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods: A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results: A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion: Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the combination of

  6. Diffusion tensor magnetic resonance imaging of glial brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri, E-mail: ferda@fnplzen. [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Kastner, Jan [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Mukensnabl, Petr [Sikl' s Institute of Pathological Anatomy, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Choc, Milan [Department of Neurosurgery, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Horemuzova, Jana; Ferdova, Eva; Kreuzberg, Boris [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic)

    2010-06-15

    Aim: To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods: A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results: A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion: Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the

  7. A Mathematical Model of Regenerative Axon Growing along Glial Scar after Spinal Cord Injury

    Science.gov (United States)

    Chen, Xuning; Zhu, Weiping

    2016-01-01

    A major factor in the failure of central nervous system (CNS) axon regeneration is the formation of glial scar after the injury of CNS. Glial scar generates a dense barrier which the regenerative axons cannot easily pass through or by. In this paper, a mathematical model was established to explore how the regenerative axons grow along the surface of glial scar or bypass the glial scar. This mathematical model was constructed based on the spinal cord injury (SCI) repair experiments by transplanting Schwann cells as bridge over the glial scar. The Lattice Boltzmann Method (LBM) was used in this model for three-dimensional numerical simulation. The advantage of this model is that it provides a parallel and easily implemented algorithm and has the capability of handling complicated boundaries. Using the simulated data, two significant conclusions were made in this study: (1) the levels of inhibitory factors on the surface of the glial scar are the main factors affecting axon elongation and (2) when the inhibitory factor levels on the surface of the glial scar remain constant, the longitudinal size of the glial scar has greater influence on the average rate of axon growth than the transverse size. These results will provide theoretical guidance and reference for researchers to design efficient experiments.

  8. Glial heterotopia in head and neck, single center experience of 5 cases

    Directory of Open Access Journals (Sweden)

    Ramyapriyadarshini Arikeri

    2016-07-01

    Conclusions: Glial Heterotopias of head and neck are more common in the nasal cavity. Middle ear Glial heterotopias are very rare. Clinical and radiological findings along with histopathology and immuno-histochemistry are essential in diagnosing these lesions. [Int J Res Med Sci 2016; 4(7.000: 3009-3012

  9. Morphological alterations in radial glial cells following brain injury in fetal mice

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xuezhi; Inouye, Minoru; Hayasaka, Shizu; Takagishi, Yoshiko; Yamamura, Hideki [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1995-10-01

    A glia cell population extracted from the developing brain of mice exposed to {gamma}-irradiation at a dose of 1.0 Gy on embryonic day 13 (E13) was evaluated. An immunohistochemical detection method for the anti-GFAP (glial fibrillary acidic protein) anti-body showed that the GFAP-immunoreactive fibers first appeared on E18. These radial glial fibers ran straight to the pial surface in the control, but were crumpled in the irradiated brain samples. Although some radial glial cells transformed into astrocytes over time in both the control and irradiated brains, astrocytes appeared in the irradiated brain earlier than in the control. These findings indicate that 1.0 Gy {gamma}-irradiation causes radial glial fibers to crumple and could affect the transformation process whereby radial glial cells develop into astrocytes. (author).

  10. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    International Nuclear Information System (INIS)

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system

  11. Morphological alterations in radial glial cells following brain injury in fetal mice

    International Nuclear Information System (INIS)

    A glia cell population extracted from the developing brain of mice exposed to γ-irradiation at a dose of 1.0 Gy on embryonic day 13 (E13) was evaluated. An immunohistochemical detection method for the anti-GFAP (glial fibrillary acidic protein) anti-body showed that the GFAP-immunoreactive fibers first appeared on E18. These radial glial fibers ran straight to the pial surface in the control, but were crumpled in the irradiated brain samples. Although some radial glial cells transformed into astrocytes over time in both the control and irradiated brains, astrocytes appeared in the irradiated brain earlier than in the control. These findings indicate that 1.0 Gy γ-irradiation causes radial glial fibers to crumple and could affect the transformation process whereby radial glial cells develop into astrocytes. (author)

  12. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  13. Sox2 promotes survival of satellite glial cells in vitro

    International Nuclear Information System (INIS)

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling

  14. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  15. How do glial cells contribute to motor control?

    DEFF Research Database (Denmark)

    Christensen, Rasmus Kordt; Petersen, Anders Victor; Perrier, Jean-Francois Marie

    2013-01-01

    activated by neurotransmitters during synaptic transmission. In turn they release other transmitters - called gliotransmitters - that bind to neuronal receptors and modulate synaptic transmission. This feedback, which led to the concept of the tripartite synapse, has been reported with various transmitters...... glia play an active role in several physiological functions. The discovery that a bidirectional communication takes place between astrocytes (the star shaped glial cell of the brain) and neurons, was a major breakthrough in the field of synaptic physiology. Astrocytes express receptors that get...... including glutamate, ATP, GABA or serine. In the present review we will focus on astrocytes and review the evidence suggesting and demonstrating their role in motor control. Rhythmic motor behaviors such as locomotion, swimming or chewing are generated by networks of neurons termed central pattern...

  16. Cytotoxic effects of catechols to glial and neuronal cells

    Directory of Open Access Journals (Sweden)

    Ramon Santos El-Bachá

    2015-04-01

    Full Text Available Catechols are compounds that autoxidises under physiological conditions leading to the formation of reactive oxygen species (ROS, semiquinones, and quinones. These molecules can be formed in organisms because of the metabolism of exogenous aromatic substances, such as benzene. However, there are several important endogenous catechols, which have physiological functions, such as catecholamines. Furthermore, several pharmacological agents are catechols, such as apomorphine, or can be metabolised to generate these compounds. In this presentation we will show that apomorphine can unspecifically bind to proteins during its autoxidation, a phenomenon that is inhibited by thiols. Brain endothelial cells and glial cells express xenobiotic-metabolising enzymes as components of the metabolic blood-brain barrier in an attempt to protect the central nervous system against drugs. Since UDP-glucuronosyltransferases (EC 2.4.1.17 are among these enzymes, we investigated the ability of brain microsomes to conjugate catechols with glucuronate. Despite the fact that 1-naphtol could be glucuronidated in the presence of brain cortex microsomes, the same was not observed for most of catechols that were tested. Therefore, this is not the main mechanism used to protect the brain against them. Indeed, catechols may inhibit other xenobiotic-metabolising enzymes. We showed that apomorphine inhibited the cytochrome P450-dependent dealkylation activity. The production of ROS and reactive quinones, as well as their effects on protein functions, seems to be involved in the cytotoxicity of catechols. Glial cells are more resistant than neuronal cells. Apomorphine was more toxic to rat neurons than to rat C6 glioma cells. 1,2-Dihydroxybenzene (catechol killed human GL-15 cells with an EC50 of 230 uM after 72 h, a effect that was significantly inhibited by superoxide dismutase (EC 1.15.1.1. Another mechanism that we found to be involved in catechol cytotoxicity is the inhibition

  17. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells in relation to poten...nctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. Authors Nod

  18. Depression as a Glial-Based Synaptic Dysfunction.

    Science.gov (United States)

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M; Gonçalves, Francisco Q; Real, Joana I; Prediger, Rui D; Gonçalves, Nélio; Gomes, Catarina A; Canas, Paula M; Agostinho, Paula; Cunha, Rodrigo A

    2015-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the "quad-partite" synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia "activation" in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication-such as the purinergic neuromodulation system operated by adenosine 5'-triphosphate (ATP) and adenosine-emerge as promising candidates to "re-normalize" synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to

  19. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  20. Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells.

    Science.gov (United States)

    Freitas, Hercules R; Ferraz, Gabriel; Ferreira, Gustavo C; Ribeiro-Resende, Victor T; Chiarini, Luciana B; do Nascimento, José Luiz M; Matos Oliveira, Karen Renata H; Pereira, Tiago de Lima; Ferreira, Leonardo G B; Kubrusly, Regina C; Faria, Robson X; Herculano, Anderson Manoel; Reis, Ricardo A de Melo

    2016-01-01

    Neuroglia interactions are essential for the nervous system and in the retina Müller cells interact with most of the neurons in a symbiotic manner. Glutathione (GSH) is a low-molecular weight compound that undertakes major antioxidant roles in neurons and glia, however, whether this compound could act as a signaling molecule in neurons and/or glia is currently unknown. Here we used embryonic avian retina to obtain mixed retinal cells or purified Müller glia cells in culture to evaluate calcium shifts induced by GSH. A dose response curve (0.1-10 mM) showed that 5-10 mM GSH, induced calcium shifts exclusively in glial cells (later labeled and identified as 2M6 positive cells), while neurons responded to 50 mM KCl (labeled as βIII tubulin positive cells). BBG 100 nM, a P2X7 blocker, inhibited the effects of GSH on Müller glia. However, addition of DNQX 70 μM and MK-801 20 μM, non-NMDA and NMDA blockers, had no effect on GSH calcium induced shift. Oxidized glutathione (GSSG) at 5 mM failed to induce calcium mobilization in glia cells, indicating that the antioxidant and/or structural features of GSH are essential to promote elevations in cytoplasmic calcium levels. Indeed, a short GSH pulse (60s) protects Müller glia from oxidative damage after 30 min of incubation with 0.1% H2O2. Finally, GSH induced GABA release from chick embryonic retina, mixed neuron-glia or from Müller cell cultures, which were inhibited by BBG or in the absence of sodium. GSH also induced propidium iodide uptake in Müller cells in culture in a P2X7 receptor dependent manner. Our data suggest that GSH, in addition to antioxidant effects, could act signaling calcium shifts at the millimolar range particularly in Müller glia, and could regulate the release of GABA, with additional protective effects on retinal neuron-glial circuit. PMID:27078878

  1. [Glial cells are involved in iron accumulation and degeneration of dopamine neurons in Parkinson's disease].

    Science.gov (United States)

    Xu, Hua-Min; Wang, Jun; Song, Ning; Jiang, Hong; Xie, Jun-Xia

    2016-08-25

    A growing body of evidence suggests that glial cells play an important role in neural development, neural survival, nerve repair and regeneration, synaptic transmission and immune inflammation. As the highest number of cells in the central nervous system, the role of glial cells in Parkinson's disease (PD) has attracted more and more attention. It has been confirmed that nigral iron accumulation contributes to the death of dopamine (DA) neurons in PD. Until now, most researches on nigral iron deposition in PD are focusing on DA neurons, but in fact glial cells in the central nervous system also play an important role in the regulation of iron homeostasis. Therefore, this review describes the role of iron metabolism of glial cells in death of DA neurons in PD, which could provide evidence to reveal the mechanisms underlying nigral iron accumulation of DA neurons in PD and provide the basis for discovering new potential therapeutic targets for PD. PMID:27546505

  2. A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

    KAUST Repository

    Elsayed, Maha

    2015-12-16

    Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

  3. In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1H-[13C] MRS at 14.1T.

    Science.gov (United States)

    Lanz, Bernard; Xin, Lijing; Millet, Philippe; Gruetter, Rolf

    2014-01-01

    Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo (13) C NMR spectroscopy coupled with the infusion labeled glial-specific substrate, such as acetate. In this study, we infused alpha-chloralose anesthetized rats with [2-(13) C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using (1) H-[(13) C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two-compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid (TCA) cycle rate (Vg ) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (VNT ) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR. Pyruvate carboxylase (VPC ) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (Vx (g) and Vx (n) ) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations. In this (13) C-acetate labeling study, we propose a refined two-compartment analysis of brain energy metabolism based on (13) C turnover curves of acetate, glutamate and glutamine measured with state of the art in vivo dynamic MRS at high magnetic field in rats, enabling a deeper understanding of the specific role of glial cells in brain oxidative metabolism. In addition, the robustness of the metabolic fluxes determination relative to MRS data quality was carefully studied. PMID:24117599

  4. Defective Glial Maturation in Vanishing White Matter Disease

    Science.gov (United States)

    Bugiani, Marianna; Boor, Ilja; van Kollenburg, Barbara; Postma, Nienke; Polder, Emiel; van Berkel, Carola; van Kesteren, Ronald E.; Windrem, Martha S.; Hol, Elly M.; Scheper, Gert C.; Goldman, Steven A.; van der Knaap, Marjo S.

    2014-01-01

    Vanishing white matter disease (VWM) is a genetic leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B (eIF2B). It is a disease of infants, children and adults, who experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress and eventually leading to death. Characteristic neuropathological findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes, and paucity of myelin despite an increase in oligodendrocytic density. To assess whether a defective maturation of macroglia may be responsible for the feeble gliosis and lack of myelin, we investigated the maturation status of astrocytes and oligodendrocytes in the brains of 8 VWM patients, 4 patients with other white matter disorders and 6 age-matched controls with a combination of immunocytochemistry, histochemistry, scratch-wound assays, Western blot and quantitative PCR. We observed increased proliferation and a defect in the maturation of VWM astrocytes. They show an anomalous composition of their intermediate filament network with predominance of the δ-isoform of the glial fibrillary acidic protein and an increase in the heat shock protein αB-crystallin, supporting the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM. We also demonstrated a significant increase in numbers of pre-myelinating oligodendrocyte progenitors in VWM, which may explain the co-existence of oligodendrocytosis and myelin paucity in the patients’ white matter. PMID:21157376

  5. Endothelium in brain: Receptors, mitogenesis, and biosynthesis in glial cells

    Energy Technology Data Exchange (ETDEWEB)

    MacCumber, M.W.; Ross, C.A.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-03-01

    The authors have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice was well as primary and continuous cell cultures. A glial role is favored by several observations: (1) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C{sub 6} glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C{sub 6} glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.

  6. A Digital Realization of Astrocyte and Neural Glial Interactions.

    Science.gov (United States)

    Hayati, Mohsen; Nouri, Moslem; Haghiri, Saeed; Abbott, Derek

    2016-04-01

    The implementation of biological neural networks is a key objective of the neuromorphic research field. Astrocytes are the largest cell population in the brain. With the discovery of calcium wave propagation through astrocyte networks, now it is more evident that neuronal networks alone may not explain functionality of the strongest natural computer, the brain. Models of cortical function must now account for astrocyte activities as well as their relationships with neurons in encoding and manipulation of sensory information. From an engineering viewpoint, astrocytes provide feedback to both presynaptic and postsynaptic neurons to regulate their signaling behaviors. This paper presents a modified neural glial interaction model that allows a convenient digital implementation. This model can reproduce relevant biological astrocyte behaviors, which provide appropriate feedback control in regulating neuronal activities in the central nervous system (CNS). Accordingly, we investigate the feasibility of a digital implementation for a single astrocyte constructed by connecting a two coupled FitzHugh Nagumo (FHN) neuron model to an implementation of the proposed astrocyte model using neuron-astrocyte interactions. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed neuron astrocyte model, with significantly low hardware cost, can mimic biological behavior such as the regulation of postsynaptic neuron activity and the synaptic transmission mechanisms. PMID:26390499

  7. High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.

    Science.gov (United States)

    Bouvier, David S; Jones, Emma V; Quesseveur, Gaël; Davoli, Maria Antonietta; A Ferreira, Tiago; Quirion, Rémi; Mechawar, Naguib; Murai, Keith K

    2016-01-01

    Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research. PMID:27090093

  8. Proliferation of differentiated glial cells in the brain stem.

    Science.gov (United States)

    Barradas, P C; Cavalcante, L A

    1998-02-01

    Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions. PMID:9686148

  9. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    Barradas P.C.

    1998-01-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  10. Visualizing the Live Drosophila Glial-neuromuscular Junction with Fluorescent Dyes

    OpenAIRE

    Brink, Dee; Gilbert, Mary; Auld, Vanessa

    2009-01-01

    Our project identified GFP labeled glial structures at the developing larval fly neuromuscular synapse. To look at development of live glial-nerve-muscle synapses, we developed a larval tissue preparation that had features of live intact larvae, but also had good optical properties. This new preparation also allowed for access of perfusates to the synapse. We used fly larvae, immersed them in artificial hemolymph, and relaxed their normal rhythmic body contractions by chilling them. Next we d...

  11. Two forms of cerebellar glial cells interact differently with neurons in vitro

    OpenAIRE

    1984-01-01

    Specific interactions between neurons and glia dissociated from early postnatal mouse cerebellar tissue were studied in vitro by indirect immunocytochemical staining with antisera raised against purified glial filament protein, galactocerebroside, and the NILE glycoprotein. Two forms of cells were stained with antisera raised against purified glial filament protein. The first, characterized by a cell body 9 microns diam and processes 130-150 microns long, usually had two to three neurons asso...

  12. Glial cell modulators attenuate methamphetamine self-administration in the rat

    OpenAIRE

    SNIDER, Sarah E.; Hendrick, Elizabeth S; BEARDSLEY, PATRICK M.

    2013-01-01

    Neuroinflammation induced by activated microglia and astrocytes can be elicited by drugs of abuse. Methamphetamine administration activates glial cells and increases proinflammatory cytokine production, and there is recent evidence of a linkage between glial cell activation and drug abuse-related behavior. We have previously reported that ibudilast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), which inhibits phosphodiesterase (PDE) and pro-inflammatory activity, blocks reinstatem...

  13. Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation

    OpenAIRE

    Du, Jie; Gao, Xiaoqing; Deng, Li; Chang, Nengbin; Xiong, Huailin; Zheng, Yu

    2014-01-01

    Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, microtubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the supernatant were significantly hig...

  14. On the morphogenesis of glial compartments in the sensory organs of Caenorhabditis elegans

    OpenAIRE

    Oikonomou, Grigorios; Shaham, Shai

    2012-01-01

    Glial cells surround neuronal endings and isolate them within specialized compartments. This architecture is found at synapses in the central nervous system, as well as at receptive endings of sensory neurons. Recent studies are beginning to uncover the contributions of glial compartments to the functions of the ensheathed neurons. However, the cellular and molecular processes that guide compartment morphogenesis remain unknown. The main sensory organ of Caenorhabditis elegans, the amphid, pr...

  15. Glial protein S100B modulates long-term neuronal synaptic plasticity

    OpenAIRE

    NISHIYAMA, HIROSHI; Knöpfel, Thomas; Endo, Shogo; Itohara, Shigeyoshi

    2002-01-01

    Glial cells are traditionally regarded as elements for structural support and ionic homeostasis, but have recently attracted attention as putative integral elements of the machinery involved in synaptic transmission and plasticity. Here, we demonstrate that calcium-binding protein S100B, which is synthesized in considerable amounts in astrocytes (a major glial cell subtype), modulates long-term synaptic plasticity. Mutant mice devoid of S100B developed normally and had no detectable abnormali...

  16. Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells

    Science.gov (United States)

    Kovaleva, V. D.; Uzdensky, A. B.

    2016-04-01

    Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.

  17. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-07-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of /sup 125/I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of /sup 125/I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of /sup 125/I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence (/sup 3/H) norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors.

  18. The involvement of NF-κB in PDT-induced death of crayfish glial and nerve cells

    Science.gov (United States)

    Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.

    2015-03-01

    Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-κB in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-κB modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-κB during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-κB during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-κB modulators on photosensitized neurons and glial cells indicates the difference in NF-κB-mediated signaling pathways in these cell types. Thus, NF-κB is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.

  19. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  20. Viscoelastic properties of individual glial cells and neurons in the CNS.

    Science.gov (United States)

    Lu, Yun-Bi; Franze, Kristian; Seifert, Gerald; Steinhäuser, Christian; Kirchhoff, Frank; Wolburg, Hartwig; Guck, Jochen; Janmey, Paul; Wei, Er-Qing; Käs, Josef; Reichenbach, Andreas

    2006-11-21

    One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word "gammalambdaiotaalpha" means "glue") or provide a robust scaffold for them ("support cells"). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (i) in all CNS cells the elastic behavior dominates over the viscous behavior, (ii) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (iii) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft ("rubber elastic"), and (iv) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity. PMID:17093050

  1. The neurosteroid allopregnanolone modulates specific functions in central and peripheral glial cells

    Directory of Open Access Journals (Sweden)

    ValerioMagnaghi

    2011-12-01

    Full Text Available Since the first observations on the existence of “neurosteroids” in the 1980’s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues.

  2. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  3. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    International Nuclear Information System (INIS)

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 μM met-enkephalin, 1 μM met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined [3H]-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in [3H]-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture

  4. Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila.

    Science.gov (United States)

    Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng

    2014-02-18

    Neurons rely on glia to recycle neurotransmitters such as glutamate and histamine for sustained signaling. Both mammalian and insect glia form intercellular gap-junction networks, but their functional significance underlying neurotransmitter recycling is unknown. Using the Drosophila visual system as a genetic model, here we show that a multicellular glial network transports neurotransmitter metabolites between perisynaptic glia and neuronal cell bodies to mediate long-distance recycling of neurotransmitter. In the first visual neuropil (lamina), which contains a multilayer glial network, photoreceptor axons release histamine to hyperpolarize secondary sensory neurons. Subsequently, the released histamine is taken up by perisynaptic epithelial glia and converted into inactive carcinine through conjugation with β-alanine for transport. In contrast to a previous assumption that epithelial glia deliver carcinine directly back to photoreceptor axons for histamine regeneration within the lamina, we detected both carcinine and β-alanine in the fly retina, where they are found in photoreceptor cell bodies and surrounding pigment glial cells. Downregulating Inx2 gap junctions within the laminar glial network causes β-alanine accumulation in retinal pigment cells and impairs carcinine synthesis, leading to reduced histamine levels and photoreceptor synaptic vesicles. Consequently, visual transmission is impaired and the fly is less responsive in a visual alert analysis compared with wild type. Our results suggest that a gap junction-dependent laminar and retinal glial network transports histamine metabolites between perisynaptic glia and photoreceptor cell bodies to mediate a novel, long-distance mechanism of neurotransmitter recycling, highlighting the importance of glial networks in the regulation of neuronal functions. PMID:24550312

  5. Glial modulation by N-acylethanolamides in brain injury and neurodegeneration

    Directory of Open Access Journals (Sweden)

    María Inés Herrera

    2016-04-01

    Full Text Available Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs, naturally occurring amides, are known for their pro-homeostatic effects. An increase of NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.

  6. Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

    Science.gov (United States)

    Herrera, María I.; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

    2016-01-01

    Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells. PMID:27199733

  7. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G;

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic e...

  8. Postnatal development of the myenteric glial network and its modulation by butyrate.

    Science.gov (United States)

    Cossais, François; Durand, Tony; Chevalier, Julien; Boudaud, Marie; Kermarrec, Laetitia; Aubert, Philippe; Neveu, Isabelle; Naveilhan, Philippe; Neunlist, Michel

    2016-06-01

    The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development. PMID:27056724

  9. Cinnamon Polyphenols Attenuate Neuronal Death and Glial Swelling in Ischemic Injury

    Science.gov (United States)

    Brain edema is a major complication associated with ischemic stroke and is characterized by a volumetric enlargement of the brain. Astrocyte swelling is a major component of brain edema. We investigated the protective effects of polyphenols isolated from green tea and cinnamon in C6 glial cultures s...

  10. CONCENTRATION OF GLIAL FIBRILLARY ACIDIC PROTEIN INCREASES WITH AGE IN THE MOUSE AND RAT BRAIN

    Science.gov (United States)

    The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. n both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. he largest increase (2-fold) was observed in striatum for both...

  11. INCREASE IN GLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWS BRAIN HYPERTHERMIA IN RATS

    Science.gov (United States)

    Previously, the authors have demonstrated that an increase in the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), accompanies brain injury induced by a variety of chemical insults. In the present study the authors examined the effects of microwave-induced hy...

  12. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos

    International Nuclear Information System (INIS)

    An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms

  13. Potential primary roles of glial cells in the mechanisms of psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYamamuro

    2015-05-01

    Full Text Available While neurons have long been considered the major player in multiple brain functions such as perception, emotion and memory, glial cells have been relegated to a far lesser position, acting as merely a glue to support neurons. Multiple lines of recent evidence however, have revealed that glial cells such as oligodendrocytes, astrocytes and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g. through neurotransmitters, neurotrophic factors and cytokines and physically (e.g. through gap junctions, supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia.

  14. Potential primary roles of glial cells in the mechanisms of psychiatric disorders.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Kimoto, Sohei; Rosen, Kenneth M; Kishimoto, Toshifumi; Makinodan, Manabu

    2015-01-01

    While neurons have long been considered the major player in multiple brain functions such as perception, emotion, and memory, glial cells have been relegated to a far lesser position, acting as merely a "glue" to support neurons. Multiple lines of recent evidence, however, have revealed that glial cells such as oligodendrocytes, astrocytes, and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g., through neurotransmitters, neurotrophic factors, and cytokines) and physically (e.g., through gap junctions), supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia. PMID:26029044

  15. Controlled adhesion and growth of long term glial and neuronal cultures on Parylene-C.

    Directory of Open Access Journals (Sweden)

    Evangelos Delivopoulos

    Full Text Available This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO(2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1-P7 rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF. We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures.

  16. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence.

    Science.gov (United States)

    Ibiza, Sales; García-Cassani, Bethania; Ribeiro, Hélder; Carvalho, Tânia; Almeida, Luís; Marques, Rute; Misic, Ana M; Bartow-McKenney, Casey; Larson, Denise M; Pavan, William J; Eberl, Gérard; Grice, Elizabeth A; Veiga-Fernandes, Henrique

    2016-07-21

    Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers. ILC3 development is thought to be programmed, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals. PMID:27409807

  17. Involvement of interleukin-1 in glial responses to lipopolysaccharide: endogenous versus exogenous interleukin-1 actions.

    Science.gov (United States)

    Molina-Holgado, F; Toulmond, S; Rothwell, N J

    2000-11-01

    Interleukin-1beta (IL-1beta) participates in neuroinflammation and neurodegeneration. Its mechanisms of action are not fully understood, but appear to involve complex interactions between neurons and glia. The objective of this study was to determine the involvement of endogenous IL-1beta in inflammatory responses to LPS in cultured mouse glial cells, and compare this to the effects of exogenous IL-1beta. Activation of primary mixed glial cultures by incubation with LPS (1 microgram/ml, 24 h), caused marked (approximately ten-fold) increases in release of NO, twenty-fold increases in PGE(2) and ninety-fold increases of IL-6 release. Incubation with human recombinant IL-1beta (100 ng/ml) also stimulated NO and IL-6 release to a similar extent to LPS, but IL-1beta (1 or 100 ng/ml) caused only modest increases (approximately seven-fold) in PGE(2) release. Co-incubation with IL-1ra inhibited the effects of LPS on NO release (-65%) and IL-6 production (-30%), but failed to reduce PGE(2) release. These results indicate that exogenous IL-1beta induces release of NO, PGE(2) and IL-6 in mixed glial cultures, and that endogenous IL-1beta mediates inflammatory actions of LPS on NO and to a lesser extent IL-6, but not on PGE(2) release in mixed glial cultures. Indeed endogenous IL-1beta appears to inhibit LPS-induced PGE(2) release. PMID:11063815

  18. Effects of estrogen on collagen gel contraction by human retinal glial cells

    Institute of Scientific and Technical Information of China (English)

    QIU Qing-hua; CHEN Zhi-Yi; YIN Li-li; ZHENG Zhi; WU Xing-wei

    2012-01-01

    Background There are definite gender differences in patients with macular holes.Menopausal women over 50 years are most affected.We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells.It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.Methods Estrogen was used to determine its effects on collagen gel contraction,and its function was measured using morphological changes in cells.Human retinal glial cells were cultured in collagen solution.The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.Results Estrogen at differing concentrations had no effect on the growth of human retinal glial cells.However,after exposed to collagen gel block,less contraction was noted in the estrogen-treated group than in the control group.Conclusions Estrogen can inhibit collagen gel contraction by glial cells.These results suggest a mechanism for macular hole formation,which is observed in menopausal females.

  19. Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila

    OpenAIRE

    Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng

    2014-01-01

    Neurons communicate at synapses through neurotransmitters. For sustained neuronal signaling, neurotransmitters are recycled after release from neuronal terminals. During this process, perisynaptic glial cells take in and convert neurotransmitters such as glutamate, GABA, and histamine into inactive metabolites for transport. It has been assumed that inactive metabolites are delivered directly into neighboring neuronal terminals for neurotransmitter regeneration. Our work in the fruit fly, how...

  20. Fascin expression [corrected] in glial tumors and its prognostic significance in glioblastomas.

    Science.gov (United States)

    Gunal, Armagan; Onguru, Onder; Safali, Mukerrem; Beyzadeoglu, Murat

    2008-08-01

    Fascin is a -55 kDa-actin binding protein. Actin bundles rearranged by fascin proteins are concentrated in cell membrane protrusions and these protrusions provide motility of the cell. In this study, we evaluated fascin expression in glial tumors and its relation with histologic grade. Its prognostic value in glioblastomas (GBs) was also investigated. Seventy-six glial tumors including 44 glioblastomas with known survival time, 18 anaplastic astrocytomas (AAs), six diffuse astrocytomas (DAs), and eight pilocytic astrocytomas (PAs) were examined immunohistochemically for fascin expression. Fascin was observed in the neurons of normal brain tissue and endothelium of vascular spaces in the glial tumors. Fascin expression was correlated with histologic grade in DAs. PAs expressed low levels of fascin. Half of the GBs showed high levels of fascin expression. In the GB group, overall survival was poor for cases with percentage of stained cells >50% having moderate or strong staining intensity. In GBs, overall survival was also poor for >50-year-old cases and cases that refused radiotherapy. Multivariate Cox regression analysis revealed that age (>50 years, P=0.021) and higher level of fascin expression (immunohistochemical score >8, P=0.040) were independent poor prognostic factors. In conclusion, fascin expression levels are correlated with histologic grade and fascin overexpression may play an important role in the biologic behavior of glial astrocytic tumors and in the prognosis of GBs. PMID:18298442

  1. A New CRB1 Rat Mutation Links Müller Glial Cells to Retinal Telangiectasia

    NARCIS (Netherlands)

    Zhao, Min; Andrieu-Soler, Charlotte; Kowalczuk, Laura; Paz Cortés, María; Berdugo, Marianne; Dernigoghossian, Marilyn; Halili, Francisco; Jeanny, Jean-Claude; Goldenberg, Brigitte; Savoldelli, Michèle; El Sanharawi, Mohamed; Naud, Marie-Christine; van Ijcken, Wilfred; Pescini-Gobert, Rosanna; Martinet, Danielle; Maass, Alejandro; Wijnholds, J.; Crisanti, Patricia; Rivolta, Carlo; Behar-Cohen, Francine

    2015-01-01

    We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacT

  2. A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia

    NARCIS (Netherlands)

    M. Zhao (Min); C. Andrieu-Soler (Charlotte); L. Kowalczuk (Laura); M.P. Cortés (María Paz); M. Berdugo (Marianne); M. Dernigoghossian (Marilyn); F. Halili (Francisco); J.-C. Jeanny (Jean-Claude); B. Goldenberg (Brigitte); M. Savoldelli (Michèle); M. El Sanharawi (Mohamed); M.-C. Naud (Marie-Christine); W.F.J. van IJcken (Wilfred); R. Pescini-Gobert (Rosanna); D. Martinet (Danielle); A. Maass (Alejandro); J. Wijnholds (Jan); P. Crisanti (Patricia); C. Rivolta (Carlo); F. Behar-Cohen (Francine)

    2015-01-01

    textabstractWe have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia

  3. Multiscale Vision Model Highlights Spontaneous Glial Calcium Waves Recorded by 2-Photon Imaging in Brain Tissue

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Mathiesen, Claus; Lauritzen, Martin

    2013-01-01

    Intercellular glial calcium waves constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca2+ changes. However, there is a lack of procedures for sensitive and reliable detection of calcium waves in noisy multiphoton imaging data. Here we extend multiscale vis...

  4. Microbiota controls the homeostasis of glial cells in the gut lamina propria

    NARCIS (Netherlands)

    Kabouridis, Panagiotis S; Lasrado, Reena; McCallum, Sarah; Chng, Song Hui; Snippert, HJG; Clevers, Hans; Pettersson, Sven; Pachnis, Vassilis

    2015-01-01

    The intrinsic neural networks of the gastrointestinal tract are derived from dedicated neural crest progenitors that colonize the gut during embryogenesis and give rise to enteric neurons and glia. Here, we study how an essential subpopulation of enteric glial cells (EGCs) residing within the intest

  5. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge;

    2003-01-01

    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

  6. Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn.

    Science.gov (United States)

    Jiang, Enshe; Yan, Xisheng; Weng, Han-Rong

    2012-05-01

    Decreased GABAergic synaptic strength ('disinhibition') in the spinal dorsal horn is a crucial mechanism contributing to the development and maintenance of pathological pain. However, mechanisms leading to disinhibition in the spinal dorsal horn remain elusive. We investigated the role of glial glutamate transporters (GLT-1 and GLAST) and glutamine synthetase in maintaining GABAergic synaptic activity in the spinal dorsal horn. Electrically evoked GABAergic inhibitory post-synaptic currents (eIPSCs), spontaneous IPSCs (sIPSCs) and miniature IPSCs were recorded in superficial spinal dorsal horn neurons of spinal slices from young adult rats. We used (2S,3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), to block both GLT-1 and GLAST and dihydrokainic acid to block only GLT-1. We found that blockade of both GLAST and GLT-1 and blockade of only GLT-1 in the spinal dorsal horn decreased the amplitude of GABAergic eIPSCs, as well as both the amplitude and frequency of GABAergic sIPSCs or miniature IPSCs. Pharmacological inhibition of glial glutamine synthetase had similar effects on both GABAergic eIPSCs and sIPSCs. We provided evidence demonstrating that the reduction in GABAergic strength induced by the inhibition of glial glutamate transporters is due to insufficient GABA synthesis through the glutamate-glutamine cycle between astrocytes and neurons. Thus, our results indicate that deficient glial glutamate transporters and glutamine synthetase significantly attenuate GABAergic synaptic strength in the spinal dorsal horn, which may be a crucial synaptic mechanism underlying glial-neuronal interactions caused by dysfunctional astrocytes in pathological pain conditions. PMID:22339645

  7. Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat.

    Science.gov (United States)

    Lee, Hee Jae; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel

    2016-07-01

    Valproic acid (VPA) is a neurotherapeutic drug prescribed for seizures, bipolar disorder, and migraine, including women of reproductive age. VPA is a well-known teratogen that produces congenital malformations in many organs including the nervous system, as well as later neurodevelopmental disorders, including mental retardation and autism. In developing brain, few studies have examined VPA effects on glial cells, particularly astrocytes. To investigate effects on primary glial precursors, we developed new cell culture and in vivo models using frontal cerebral cortex of postnatal day (P2) rat. In vitro, VPA exposure elicited dose-dependent, biphasic effects on DNA synthesis and proliferation. In vivo VPA (300 mg/kg) exposure from P2 to P4 increased both DNA synthesis and cell proliferation, affecting primarily astrocyte precursors, as >75% of mitotic cells expressed brain lipid-binding protein. Significantly, the consequence of early VPA exposure was increased astrocytes, as both S100-β+ cells and glial fibrillary acidic protein were increased in adolescent brain. Molecularly, VPA served as an HDAC inhibitor in vitro and in vivo as enhanced proliferation was accompanied by increased histone acetylation, whereas it elicited changes in culture in cell-cycle regulators, including cyclin D1 and E, and cyclin-dependent kinase (CDK) inhibitors, p21 and p27. Collectively, these data suggest clinically relevant VPA exposures stimulate glial precursor proliferation, though at higher doses can elicit inhibition through differential regulation of CDK inhibitors. Because changes in glial cell functions are proposed as mechanisms contributing to neuropsychiatric disorders, these observations suggest that VPA teratogenic actions may be mediated through changes in astrocyte generation during development. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 780-798, 2016. PMID:26505176

  8. Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment.

    Science.gov (United States)

    Shi, Ming; Du, Fang; Liu, Yang; Li, Li; Cai, Jing; Zhang, Guo-Feng; Xu, Xiao-Fei; Lin, Tian; Cheng, Hao-Ran; Liu, Xue-Dong; Xiong, Li-Ze; Zhao, Gang

    2013-11-01

    Vibroacoustic disease, a progressive and systemic disease, mainly involving the central nervous system, is caused by excessive exposure to low-frequency but high-intensity noise generated by various heavy transportations and machineries. Infrasound is a type of low-frequency noise. Our previous studies demonstrated that infrasound at a certain intensity caused neuronal injury in rats but the underlying mechanism(s) is still largely unknown. Here, we showed that glial cell-expressed TRPV4, a Ca(2+)-permeable mechanosensitive channel, mediated infrasound-induced neuronal injury. Among different frequencies and intensities, infrasound at 16 Hz and 130 dB impaired rat learning and memory abilities most severely after 7-14 days exposure, a time during which a prominent loss of hippocampal CA1 neurons was evident. Infrasound also induced significant astrocytic and microglial activation in hippocampal regions following 1- to 7-day exposure, prior to neuronal apoptosis. Moreover, pharmacological inhibition of glial activation in vivo protected against neuronal apoptosis. In vitro, activated glial cell-released proinflammatory cytokines IL-1β and TNF-α were found to be key factors for this neuronal apoptosis. Importantly, infrasound induced an increase in the expression level of TRPV4 both in vivo and in vitro. Knockdown of TRPV4 expression by siRNA or pharmacological inhibition of TRPV4 in cultured glial cells decreased the levels of IL-1β and TNF-α, attenuated neuronal apoptosis, and reduced TRPV4-mediated Ca(2+) influx and NF-κB nuclear translocation. Finally, using various antagonists we revealed that calmodulin and protein kinase C signaling pathways were involved in TRPV4-triggered NF-κB activation. Thus, our results provide the first evidence that glial cell-expressed TRPV4 is a potential key factor responsible for infrasound-induced neuronal impairment. PMID:24002225

  9. Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect

    International Nuclear Information System (INIS)

    Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain. Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons

  10. Emerging role of glial cells in the control of body weight

    Science.gov (United States)

    García-Cáceres, Cristina; Fuente-Martín, Esther; Argente, Jesús; Chowen, Julie A.

    2012-01-01

    Glia are the most abundant cell type in the brain and are indispensible for the normal execution of neuronal actions. They protect neurons from noxious insults and modulate synaptic transmission through affectation of synaptic inputs, release of glial transmitters and uptake of neurotransmitters from the synaptic cleft. They also transport nutrients and other circulating factors into the brain thus controlling the energy sources and signals reaching neurons. Moreover, glia express receptors for metabolic hormones, such as leptin and insulin, and can be activated in response to increased weight gain and dietary challenges. However, chronic glial activation can be detrimental to neurons, with hypothalamic astrocyte activation or gliosis suggested to be involved in the perpetuation of obesity and the onset of secondary complications. It is now accepted that glia may be a very important participant in metabolic control and a possible therapeutical target. Here we briefly review this rapidly advancing field. PMID:24024117

  11. Induction of the major heat-stress protein in purified rat glial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, R.N.; Dwyer, B.E.; Welch, W.; Cole, R.; de Vellis, J.; Liotta, K.

    1988-05-01

    Cultured purified oligodendroglia and astroglia exposed to heat stress (45 degrees C, 10 or 20 min) synthesized a 68-kDa heat-stress protein, which migrates on two-dimensional gel electrophoresis and reacts with a specific monoclonal antibody suggesting it is similar to a major 72-kDa heat-shock protein previously reported in other cell types. This protein was not detected in control glial cultures. Actinomycin D prevented synthesis of this protein demonstrating an absolute requirement for newly synthesized mRNA. The response was prolonged by increasing the period of heat stress from 10 to 20 min. In addition to the 68-kDa HSP protein, the incorporation of radioactivity into 70-, 89-, and 97-kDa proteins was also increased after heating, but in contrast to the 68 kDa protein these proteins appeared to be made in control glial cultures.

  12. [State of the blood coagulation in glial tumors of the brain].

    Science.gov (United States)

    Burgman, G P; Kachkov, I A; Vial'tseva, I N; Shcherbakova, G G

    1979-01-01

    The data presented may be of definite value in the prevention of hemorrhage and thrombosis in patients with malignant glial tumors. A malignant glioma may lead to increased activity of the blood coagulation system (BCS). Preoperative staining of the tumor was not attended by marked changes in the BCS and blood viscocity, though a tendency towards an increase in BCS activity according to some of the indices may sometimes be noted. Chemotherapy with nitrosourea and methotrexate was attended by thrombocytopenia but there was practically no changes in the other BCS indices. The postoperative period is usually marked by increased BCS activity according to most of the indices. Increased blood viscocity is often encountered in patients with glial cerebral tumors in the preoperative and postoperative periods, which is evidently due to the intensive dehydration therapy to which they are subjected in marked increase of intracranial pressure. PMID:223352

  13. Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies

    Institute of Scientific and Technical Information of China (English)

    Gabrio Bassotti; Vincenzo Villanacci; Simona Fisogni; Elisa Rossi; Paola Baronio; Carlo Clerici; Christoph A Maurer; Gieri Cathomas; Elisabetta Antonelli

    2007-01-01

    The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently,some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neurogliopathies.

  14. Crosslinked gelatin nanofibres: Preparation, characterisation and in vitro studies using glial-like cells

    International Nuclear Information System (INIS)

    Gelatin (GL) nanofibrous matrices mimicking the complex biological structure of the natural extracellular matrix (ECM) were prepared from aqueous solutions by electrospinning technique. GL nanofibres with a diameter size of around 300 nm were obtained optimising the process and solution parameters. To increase the GL stability in aqueous environment γ-glycidoxypropyltrimethoxysilane (GPTMS) was used as GL crosslinker. GPTMS crosslinking did not modify the nanofibrous matrix morphology: fibre diameter and membrane pores size were 327 ± 45 nm and 1.64 ± 0.37 μm, respectively. The produced GPTMS crosslinked GL nanofibres (GL/GPTMSNF) were found to support the in vitro adhesion, proliferation and survival of neonatal olfactory bulb ensheating cells (NOBECs). - Highlights: • Gelatin nanofibres were prepared from aqueous solution. • A silane-coupling agent was used as gelatin crosslinker. • Glial-like cells adhered and proliferated on the developed nanofibres. • Elongated morphology of glial-like cells was observed

  15. Neural stem cell activation and glial proliferation in the hippocampal CA3 region of posttraumatic epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Yuanxiang Lin; Kun Lin; Dezhi Kang; Feng Wang

    2011-01-01

    The present study observed the dynamic expression of CD133, nuclear factor-κB and glial fibrillary acidic protein in the hippocampal CA3 area of the experimental posttraumatic epilepsy rats to investigate whether gliosis occurs after posttraumatic epilepsy. CD133 and nuclear factor-κB expression was increased at 1 day after posttraumatic epilepsy, peaked at 7 days, and gradually decreased up to 14 days, as seen by double-immunohistochemical staining. Glial fibrillary acidic protein/nuclear factor-κB double-labeled cells increased with time and peaked at 14 days after posttraumatic epilepsy. Results show that activation of hippocampal neural stem cells and glial proliferation after posttraumatic epilepsy-induced oxidative stress increases hippocampal glial cell density.

  16. Hypothalamic Glial-to-Neuronal Signaling during Puberty: Influence of Alcohol

    OpenAIRE

    W. Les Dees; Hiney, Jill K.; Srivastava, Vinod K

    2011-01-01

    Mammalian puberty requires complex interactions between glial and neuronal regulatory systems within the hypothalamus that results in the timely increase in the secretion of luteinizing hormone releasing hormone (LHRH). Assessing the molecules required for the development of coordinated communication networks between glia and LHRH neuron terminals in the basal hypothalamus, as well as identifying substances capable of affecting cell-cell communication are important. One such pathway involves ...

  17. The impact of the glial spatial buffering on the K+ Nernst potential

    OpenAIRE

    Noori, H. R.

    2011-01-01

    Astrocytes play a critical role in CNS metabolism, regulation of volume and ion homeostasis of the interstitial space. Of special relevance is their clearance of K+ that is released by active neurons into the extracellular space. Mathematical analysis of a modified Nernst equation for the electrochemical equilibrium of neuronal plasma membranes, suggests that K+ uptake by glial cells is not only relevant during neuronal activity but also has a non-neglectable impact on the basic electrical me...

  18. White Matter Tauopathy with Globular Glial Inclusions: A Distinct Sporadic Frontotemporal Lobar Degeneration

    OpenAIRE

    Kovacs, Gabor G.; Majtenyi, Katalin; Spina, Salvatore; Murrell, Jill R; Gelpi, Ellen; Hoftberger, Romana; Fraser, Graham; Crowther, R. Anthony; Goedert, Michel; Budka, Herbert; Ghetti, Bernardino

    2008-01-01

    Frontotemporal lobar degenerations are a group of disorders characterized by circumscribed degeneration of the frontal and temporal lobes and diverse histopathological features. We report clinical, neuropathological, ultrastructural, biochemical and genetic data on seven individuals with a four-repeat (4R) tauopathy characterized by the presence of globular glial inclusions (GGIs) in brain white matter. Clinical manifestations were compatible with the behavioral variant of frontotemporal deme...

  19. Curcumin alters expression of glial fibrillary acidic protein and nestin following chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Peng Zhang; Tianping Yu; Xiong Zhang; Yu Li

    2011-01-01

    Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed that pathological changes of neuronal injury in hippocampal CA1 area of rats induced by chronic cerebral ischemia were attenuated, as well as upregulated expression of glial fibrillary acidic protein and nestin, in a dose-dependent manner.

  20. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

    OpenAIRE

    Pavel Nikolaevich Vlasov; PavelNikolayevich Vlasov; A. V. Chervyakov; S V Urakov; A A Solokha

    2009-01-01

    In growing glial tumors, epileptic seizures are the first and only symptom of the disease in more than a third of cases. The seizure is commonly characterized by only psychopathological disorders that are frequently ignored by both patients and physicians. The deja vu (DV) phenomenon may be one of such symptoms. Its specific feature is that it occurs in both healthy individuals and patients with various brain pathologies. This investigation was undertaken to study the implication of the DV...

  1. Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake

    OpenAIRE

    Beurrier, Corinne; Faideau, Mathilde; Bennouar, Khaled-Ezaheir; Escartin, Carole; Kerkerian-Le Goff, Lydia; Bonvento, Gilles; Gubellini, Paolo

    2010-01-01

    Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by ∼75%) in CNTF-treated anima...

  2. Dissociated neurons and glial cells derived from rat inferior colliculi after digestion with papain.

    Science.gov (United States)

    Kaiser, Odett; Aliuos, Pooyan; Wissel, Kirsten; Lenarz, Thomas; Werner, Darja; Reuter, Günter; Kral, Andrej; Warnecke, Athanasia

    2013-01-01

    The formation of gliosis around implant electrodes for deep brain stimulation impairs electrode-tissue interaction. Unspecific growth of glial tissue around the electrodes can be hindered by altering physicochemical material properties. However, in vitro screening of neural tissue-material interaction requires an adequate cell culture system. No adequate model for cells dissociated from the inferior colliculus (IC) has been described and was thus the aim of this study. Therefore, IC were isolated from neonatal rats (P3_5) and a dissociated cell culture was established. In screening experiments using four dissociation methods (Neural Tissue Dissociation Kit [NTDK] T, NTDK P; NTDK PN, and a validated protocol for the dissociation of spiral ganglion neurons [SGN]), the optimal media, and seeding densities were identified. Thereafter, a dissociation protocol containing only the proteolytic enzymes of interest (trypsin or papain) was tested. For analysis, cells were fixed and immunolabeled using glial- and neuron-specific antibodies. Adhesion and survival of dissociated neurons and glial cells isolated from the IC were demonstrated in all experimental settings. Hence, preservation of type-specific cytoarchitecture with sufficient neuronal networks only occurred in cultures dissociated with NTDK P, NTDK PN, and fresh prepared papain solution. However, cultures obtained after dissociation with papain, seeded at a density of 2×10(4) cells/well and cultivated with Neuro Medium for 6 days reliably revealed the highest neuronal yield with excellent cytoarchitecture of neurons and glial cells. The herein described dissociated culture can be utilized as in vitro model to screen interactions between cells of the IC and surface modifications of the electrode. PMID:24349001

  3. Glial Regulation of the Neuronal Connectome through Local and Long-Distant Communication

    OpenAIRE

    Fields, R. Douglas; Woo, Dong ho; Basser, Peter J.

    2015-01-01

    If “the connectome” represents a complete map of anatomical and functional connectivity in the brain, it should also include glia. Glia define and regulate both the brain’s anatomical and functional connectivity over a broad range of length scales, spanning the whole brain to subcellular domains of synaptic interactions. This Perspective article examines glial interactions with the neuronal connectome, including long-range networks, local circuits, and individual synaptic connections; and hig...

  4. Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus

    OpenAIRE

    Williamson, Lauren L.; Chao, Agnes; Bilbo, Staci D.

    2012-01-01

    Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Environmental enrichment (EE) in rodents increases neurogenesis, enhances cognition, and promotes recovery from injury. However, little is known about the effects of EE on glia (astrocytes and microglia). Given their importance in neural repair, we predicted that EE would modulate glial phenotype and/or function within the hippocampus. Adult male rats were housed either 12 h/day in an enric...

  5. Neuronal–glial alterations in non-primary motor areas in chronic subcortical stroke

    OpenAIRE

    Carmen M. Cirstea; Nudo, Randolph J.; Craciunas, Sorin C.; Popescu, Elena A.; Choi, In-Young; Lee, Phil; Yeh, Hung-Wen; Savage, Cary R.; Brooks, William M.

    2012-01-01

    Whether functional changes of the non-primary motor areas, e.g., dorsal premotor (PMd) and supplementary motor (SMA) areas, after stroke, reflect reorganization phenomena or recruitment of a pre-existing motor network remains to be clarified. We hypothesized that cellular changes in these areas would be consistent with their involvement in post-stroke reorganization. Specifically, we expected that neuronal and glial compartments would be altered in radiologically normal-appearing, i.e., spare...

  6. Roscovitine reduces neuronal loss, glial activation and neurological deficits after brain trauma

    OpenAIRE

    Hilton, Genell D.; Stoica, Bogdan A.; Byrnes, Kimberly R.; Faden, Alan I.

    2008-01-01

    TBI causes both direct and delayed tissue damage. The latter is associated with secondary biochemical changes such as cell cycle activation that lead to neuronal death, inflammation and glial scarring. Flavopiridol — a CDK inhibitor that is neither specific nor selective — is neuroprotective. To examine the role of more specific CDK inhibitors as potential neuroprotective agents, we studied the effects of roscovitine in TBI. Central administration of roscovitine 30 minutes after injury result...

  7. Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

    OpenAIRE

    Morel, Gustavo R.; Sosa, Yolanda E.; Bellini, Maria J.; Carri, Nestor G.; Rodriguez, Silvia S.; Bohn, Martha C.; Goya, Rodolfo G.

    2010-01-01

    Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (1010 pfu) of either an adenovir...

  8. Sudden death due to a glial cyst of the pineal gland.

    OpenAIRE

    Milroy, C M; Smith, C.L.

    1996-01-01

    Asymptomatic cysts of the pineal gland are found frequently by radiological examination of the brain or at postmortem examination. Symptomatic cysts are rare, and may require surgical intervention. Sudden death due to a cystic lesion of the pineal gland is very rare. A case of a 22 year old man who collapsed and died unexpectedly is reported. Postmortem examination revealed a glial cyst of the pineal gland and evidence of chronic obstructive hydrocephalus. Deaths from colloid cysts and pineal...

  9. Time-lapse imaging reveals stereotypical patterns of Drosophila midline glial migration.

    Science.gov (United States)

    Wheeler, Scott R; Pearson, Joseph C; Crews, Stephen T

    2012-01-15

    The Drosophila CNS midline glia (MG) are multifunctional cells that ensheath and provide trophic support to commissural axons, and direct embryonic development by employing a variety of signaling molecules. These glia consist of two functionally distinct populations: the anterior MG (AMG) and posterior MG (PMG). Only the AMG ensheath axon commissures, whereas the function of the non-ensheathing PMG is unknown. The Drosophila MG have proven to be an excellent system for studying glial proliferation, cell fate, apoptosis, and axon-glial interactions. However, insight into how AMG migrate and acquire their specific positions within the axon-glial scaffold has been lacking. In this paper, we use time-lapse imaging, single-cell analysis, and embryo staining to comprehensively describe the proliferation, migration, and apoptosis of the Drosophila MG. We identified 3 groups of MG that differed in the trajectories of their initial inward migration: AMG that migrate inward and to the anterior before undergoing apoptosis, AMG that migrate inward and to the posterior to ensheath commissural axons, and PMG that migrate inward and to the anterior to contact the commissural axons before undergoing apoptosis. In a second phase of their migration, the surviving AMG stereotypically migrated posteriorly to specific positions surrounding the commissures, and their final position was correlated with their location prior to migration. Most noteworthy are AMG that migrated between the commissures from a ventral to a dorsal position. Single-cell analysis indicated that individual AMG possessed wide-ranging and elaborate membrane extensions that partially ensheathed both commissures. These results provide a strong foundation for future genetic experiments to identify mutants affecting MG development, particularly in guidance cues that may direct migration. Drosophila MG are homologous in structure and function to the glial-like cells that populate the vertebrate CNS floorplate, and study

  10. Characterization of Olfactory Ensheathing Glial Cells Cultured on Polyurethane/Polylactide Electrospun Nonwovens

    OpenAIRE

    Jakub Grzesiak; Ryszard Fryczkowski; Anna Lis; Dariusz Szarek; Jadwiga Laska; Krzysztof Marycz

    2015-01-01

    The aim of this research was to evaluate novel biomaterials for neural regeneration. The investigated materials were composed of polyurethane (PU) and polylactide (PLDL) blended at three different w/w ratios, that is, 5/5, 6/4, and 8/2 of PU/PLDL. Ultrathin fibrous scaffolds were prepared using electrospinning. The scaffolds were investigated for their applicability for nerve regeneration by culturing rat olfactory ensheathing glial cells. Cells were cultured on the materials for seven days, ...

  11. Regulation of Nerve Growth Factor Release by Nitric Oxide through Cyclic GMP Pathway in Cortical Glial Cells

    OpenAIRE

    Xiong, Huabao; YAMADA, Kiyofumi; Jourdi, Hussam; KAWAMURA, MEIKO; TAKEI, NOBUYUKI; HAN, DAIKEN; Nabeshima, Toshitaka; Nawa, Hiroyuki

    1999-01-01

    In the present study, we found that S-nitroso-N-acetyl-dl-penicillamine, a spontaneous nitric oxide (NO) generator, dose-dependently inhibited basal nerve growth factor (NGF) release from mixed glial cells. To elucidate the function of endogenous NO in the regulation of NGF release, the mixed glial cells were stimulated with lipopolysaccharide (LPS) or LPS plus interfer-on-γ (IFNγ). The results showed that LPS alone induced NGF release and moderate NO production. However, costimulation with L...

  12. Anthocyanin Extracts from Black Soybean (Glycine max L.) Protect Human Glial Cells Against Oxygen-Glucose Deprivation by Promoting Autophagy

    OpenAIRE

    KIM, Yong Kwan; Yoon, Hye Hyeon; Lee, Young Dae; Youn, Dong-Ye; Ha, Tae Joung; Kim, Ho-Shik; Lee, Jeong-Hwa

    2012-01-01

    Anthocyanins have received growing attention as dietary antioxidants for the prevention of oxidative damage. Astrocytes, which are specialized glial cells, exert numerous essential, complex functions in both healthy and diseased central nervous system (CNS) through a process known as reactive astrogilosis. Therefore, the maintenance of glial cell viability may be important because of its role as a key modulator of neuropathological events. The aim of this study was to investigate the effect o...

  13. Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats

    OpenAIRE

    Jun, In-Gu; Kim, Sung-Hoon; Yoon, Yang-In; Park, Jong-Yeon

    2013-01-01

    Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 µg) was intrathecally injected once daily for 7 days to indu...

  14. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    OpenAIRE

    Warringa, R.A.J.; Hoeben, R C; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortis...

  15. Persistent productive infection of human glial cells by human immunodeficiency virus (HIV) and by infectious molecular clones of HIV.

    OpenAIRE

    Dewhurst, S; Sakai, K.; de Bresser, J.; Stevenson, M.; Evinger-Hodges, M J; Volsky, D J

    1987-01-01

    The nature of the interaction between human immunodeficiency virus (HIV) and human cells of astrocytic origin was studied in vitro with cultured glial cells and intact HIV or infectious molecular clones of the virus. Infection of glial cells with intact HIV was characterized by low-level expression of viral transcripts as detected by Northern blotting and in situ hybridization (less than 10 copies of HIV RNA per cell), transient virus replication, absence of viral antigens detectable by immun...

  16. The central nervous system of sea cucumbers (Echinodermata: Holothuroidea shows positive immunostaining for a chordate glial secretion

    Directory of Open Access Journals (Sweden)

    Grondona Jesus M

    2009-06-01

    Full Text Available Abstract Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS, a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common

  17. Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Corey Heffernan

    Full Text Available Multiple Sclerosis (MS is an autoimmune, neurodegenerative disease of the central nervous system (CNS characterized by demyelination through glial cell loss. Current and proposed therapeutic strategies to arrest demyelination and/or promote further remyelination include: (i modulation of the host immune system; and/or (ii transplantation of myelinating/stem or progenitor cells to the circulation or sites of injury. However, significant drawbacks are inherent with both approaches. Cell penetrating peptides (CPP are short amino acid sequences with an intrinsic ability to translocate across plasma membranes, and theoretically represent an attractive vector for delivery of therapeutic peptides or nanoparticles to glia to promote cell survival or remyelination. The CPPs described to date are commonly non-selective in the cell types they transduce, limiting their therapeutic application in vivo. Here, we describe a theoretical framework for design of a novel CPP sequence that selectively transduces human glial cells (excluding non-glial cell types, and conduct preliminary screens of purified, recombinant CPPs with immature and matured human oligodendrocytes and astrocytes, and two non-glial cell types. A candidate peptide, termed TD2.2, consistently transduced glial cells, was significantly more effective at transducing immature oligodendrocytes than matured progeny, and was virtually incapable of transducing two non-glial cell types: (i human neural cells and (ii human dermal fibroblasts. Time-lapse confocal microscopy confirms trafficking of TD2.2 (fused to EGFP to mature oligodendrocytes 3-6 hours after protein application in vitro. We propose selectivity of TD2.2 for glial cells represents a new therapeutic strategy for the treatment of glial-related disease, such as MS.

  18. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss;

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  19. Enduring Consequences of Early-Life Infection on Glial and Neural Cell Genesis Within Cognitive Regions of the Brain

    OpenAIRE

    Bland, Sondra T.; Beckley, Jacob T; Young, Sarah; Tsang, Verne; Watkins, Linda R; Steven F. Maier; Staci D. Bilbo

    2009-01-01

    Systemic infection with Escherichia coli on postnatal day (P) 4 in rats results in significantly altered brain cytokine responses and behavioral changes in adulthood, but only in response to a subsequent immune challenge with lipopolysaccharide [LPS]. The basis for these changes may be long-term changes in glial cell function. We assessed glial and neural cell genesis in the hippocampus, parietal cortex (PAR), and pre-frontal cortex (PFC), in neonates just after the infection, as well as in a...

  20. Reductions in hypothalamic Gfap expression, glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice

    OpenAIRE

    Holmes, Andrew P.; Wong, Shi Quan; Pulix, Michela; Johnson, Kirsty; Horton, Niamh S.; Thomas, Patricia; de Magalhães, João Pedro; Plagge, Antonius

    2016-01-01

    Background Neuronal and glial differentiation in the murine hypothalamus is not complete at birth, but continues over the first two weeks postnatally. Nutritional status and Leptin deficiency can influence the maturation of neuronal projections and glial patterns, and hypothalamic gliosis occurs in mouse models of obesity. Gnasxl constitutes an alternative transcript of the genomically imprinted Gnas locus and encodes a variant of the signalling protein Gαs, termed XLαs, which is expressed in...

  1. A Novel and Efficient Gene Transfer Strategy Reduces Glial Reactivity and Improves Neuronal Survival and Axonal Growth In Vitro

    OpenAIRE

    Mathieu Desclaux; Marisa Teigell; Lahouari Amar; Roland Vogel; Minerva Gimenez Y Ribotta; Alain Privat; Jacques Mallet

    2009-01-01

    Background: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both G...

  2. Tracheal development in the Drosophila brain is constrained by glial cells

    Science.gov (United States)

    Pereanu, Wayne; Spindler, Shana; Cruz, Luis; Hartenstein, Volker

    2007-01-01

    The Drosophila brain is tracheated by the cerebral trachea, a branch of the first segmental trachea of the embryo. During larval stages the cerebral trachea splits into several main (primary) branches that grow around the neuropile, forming a perineuropilar tracheal plexus (PNP) at the neuropile surface. Five primary tracheal branches whose spatial relationship to brain compartments is relatively invariant can be distinguished, although the exact trajectories and branching pattern of the brain tracheae is surprisingly variable. Immuno-histochemical and electron microscopic demonstrate that all brain tracheae grow in direct contact with the glial cell processes that surround the neuropile. To investigate the effect of glia on tracheal development, embryos and larvae lacking glial cells as a result of a genetic mutation or a directed ablation were analyzed. In these animals, the tracheal branching pattern was highly abnormal. In particular, the number of secondary branches entering the central neuropile was increased. Wild type larvae possess only two central tracheae, typically associated with the mushroom body and the antenno-cerebral tract. In larvae lacking glial cells, six to ten tracheal branches penetrate the neuropile in a variable pattern. This finding indicates that glia-derived signals constrained tracheal growth in the Drosophila brain and restrict the number of branches entering the neuropile. PMID:17046740

  3. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases.

    Science.gov (United States)

    Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario; Christofi, Fievos L

    2016-02-01

    The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential. PMID:26689598

  4. Numerical modelling and in vivo analysis of fluorescent and laser light backscattered from glial brain tumors

    Science.gov (United States)

    Savelieva, Tatiana A.; Kalyagina, Nina A.; Kholodtsova, Maria N.; Loschenov, Victor B.; Goryainov, Sergey A.; Potapov, Aleksander A.

    2012-03-01

    Brain glial tumors have peculiar features of the perifocal region extension, characterized by its indistinct area, which complicates determination of the borders for tissue resection. In the present study filter-reduced back-scattered laser light signals, compared to the data from mathematical modeling, were used for description of the brain white matter. The simulations of the scattered light distributions were performed in a Monte Carlo program using scattering and absorption parameters of the different grades of the brain glial tumors. The parameters were obtained by the Mie calculations for three main types of scatterers: myelinated axon fibers, cell nuclei and mitochondria. It was revealed that diffuse-reflected light, measured at the perifocal areas of the glial brain tumors, shows a significant difference relative to the signal, measured at the normal tissue, which signifies the possibility to provide diagnostically useful information on the tissue state, and to determine the borders of the tumor, thus to reduce the recurrence appearance. Differences in the values of ratios of diffuse reflectance from active growth parts of tumors and normal white matter can be useful for determination of the degree of tumor progress during the spectroscopic analysis.

  5. Differential effects on glial activation by a direct versus an indirect thrombin inhibitor.

    Science.gov (United States)

    Marangoni, M Natalia; Braun, David; Situ, Annie; Moyano, Ana L; Kalinin, Sergey; Polak, Paul; Givogri, Maria I; Feinstein, Douglas L

    2016-08-15

    Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS are largely unknown. In adult healthy mice, we compared the effects of treatment by the direct thrombin inhibitor dabigatran etexilate (DE), to those of warfarin, which acts by preventing vitamin K recycling essential for coagulation. After 4weeks, warfarin increased both astrocyte GFAP and microglia Iba-1 staining throughout the CNS; whereas DE reduced expression of both markers. Warfarin, but not DE, reduced sulfatide levels; and warfarin showed longer lasting changes in cerebellar gene expression. DE also reduced glial activation in a mouse model of Alzheimer's disease, although no changes in amyloid plaque burden were observed. These results suggest that treatment with direct thrombin inhibitors may be preferable to those agents which reduce vitamin K levels and have the potential to increase glial activation. PMID:27397090

  6. Etomidate reduces glutamate uptake in rat cultured glial cells: involvement of PKA

    Science.gov (United States)

    Räth, M; Föhr, K J; Weigt, H U; Gauss, A; Engele, J; Georgieff, M; Köster, S; Adolph, O

    2008-01-01

    Background and purpose: Glutamate is the main excitatory neurotransmitter in the vertebrate CNS. Removal of the transmitter from the synaptic cleft by glial and neuronal glutamate transporters (GLTs) has an important function in terminating glutamatergic neurotransmission and neurological disorders. Five distinct excitatory amino-acid transporters have been characterized, among which the glial transporters excitatory amino-acid transporter 1 (EAAT1) (glutamate aspartate transporter) and EAAT2 (GLT1) are most important for the removal of extracellular glutamate. The purpose of this study was to describe the effect of the commonly used anaesthetic etomidate on glutamate uptake in cultures of glial cells. Experimental approach: The activity of the transporters was determined electrophysiologically using the whole cell configuration of the patch-clamp recording technique. Key results: Glutamate uptake was suppressed by etomidate (3–100 μM) in a time- and concentration-dependent manner with a half-maximum effect occurring at 2.4±0.6 μM. Maximum inhibition was approximately 50% with respect to the control. Etomidate led to a significant decrease of Vmax whereas the Km of the transporter was unaffected. In all cases, suppression of glutamate uptake was reversible within a few minutes upon washout. Furthermore, both GF 109203X, a nonselective inhibitor of PKs, and H89, a selective blocker of PKA, completely abolished the inhibitory effect of etomidate. Conclusion and implications: Inhibition of glutamate uptake by etomidate at clinically relevant concentrations may affect glutamatergic neurotransmission by increasing the glutamate concentration in the synaptic cleft and may compromise patients suffering from acute or chronic neurological disorders such as CNS trauma or epilepsy. PMID:19002104

  7. Magnolol protects against trimethyltin-induced neuronal damage and glial activation in vitro and in vivo.

    Science.gov (United States)

    Kim, Da Jung; Kim, Yong Sik

    2016-03-01

    Trimethyltin (TMT), an organotin with potent neurotoxic effects by selectively damaging to hippocampus, is used as a tool for creating an experimental model of neurodegeneration. In the present study, we investigated the protective effects of magnolol, a natural biphenolic compound, on TMT-induced neurodegeneration and glial activation in vitro and in vivo. In HT22 murine neuroblastoma cells, TMT induced necrotic/apoptotic cell death and oxidative stress, including intracellular reactive oxygen species (ROS), protein carbonylation, induction of heme oxygenase-1 (HO-1), and activation of all mitogen-activated protein kinases (MAPKs) family proteins. However, magnolol treatment significantly suppressed neuronal cell death by inhibiting TMT-mediated ROS generation and activation of JNK and p38 MAPKs. In BV-2 microglial cells, magnolol efficiently attenuated TMT-induced microglial activation via suppression of ROS generation and activation of JNK, p38 MAPKs, and nuclear factor-κB (NF-κB) signaling. In an in vivo mouse study, TMT induced massive neuronal damage and enhanced oxidative stress at day 2. We also observed a concomitant increase in glial cells and inducible nitric oxide synthase (iNOS) expression on the same day. These features of TMT toxicity were reversed by treatment of magnolol. We observed that p-JNK and p-p38 MAPK levels were increased in the mouse hippocampus at day 1 after TMT treatment and that magnolol blocked TMT-induced JNK and p38 MAPK activation. Magnolol administration prevented TMT-induced hippocampal neurodegeneration and glial activation, possibly through the regulation of TMT-mediated ROS generation and MAPK activation. PMID:26756313

  8. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair.

    Directory of Open Access Journals (Sweden)

    Ravid Shechter

    Full Text Available The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL-10 producing monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG, in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13, a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This

  9. Current ideas on central chemoreception by neurons and glial cells in the retrotrapezoid nucleus

    OpenAIRE

    Mulkey, Daniel K.; Wenker, Ian C.; Kréneisz, Orsolya

    2010-01-01

    Central chemoreception is the mechanism by which CO2/pH-sensitive neurons (i.e., chemoreceptors) regulate breathing in response to changes in tissue pH. A region of the brain stem called the retrotrapezoid nucleus (RTN) is thought to be an important site of chemoreception (23), and recent evidence suggests that RTN chemoreception involves two interrelated mechanisms: H+-mediated activation of pH-sensitive neurons (38) and purinergic signaling (19), possibly from pH-sensitive glial cells. A th...

  10. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Nedergaard, S; Hansen, RR;

    2009-01-01

    of spinal cord glial activation in three different murine pain models to investigate if microglial activation is a general prerequisite for astrocyte activation in pain models. We found that two different types of cancer induced pain resulted in severe spinal astrogliosis without activation of microglia......Activation of spinal cord microglia and astrocytes is a common phenomenon in nerve injury pain models and is thought to exacerbate pain perception. Following a nerve injury, a transient increase in the presence of microglia takes place while the increased numbers of astrocytes stay elevated...

  11. Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells

    OpenAIRE

    da Silva, Larissa Bittencourt; Poulsen, Jeppe Nørgaard; Arendt-Nielsen, Lars; Gazerani, Parisa

    2015-01-01

    This study investigated the presence of cell membrane docking proteins synaptosomal-associated protein, 25 and 23 kD (SNAP-25 and SNAP-23) in satellite glial cells (SGCs) of rat trigeminal ganglion; whether cultured SGCs would release glutamate in a time- and calcium-dependent manner following calcium-ionophore ionomycin stimulation; and if botulinum neurotoxin type A (BoNTA), in a dose-dependent manner, could block or decrease vesicular release of glutamate. SGCs were isolated from the trige...

  12. Primary Glial and Neuronal Tumors of the Ovary or Peritoneum: A Clinicopathologic Study of 11 Cases.

    Science.gov (United States)

    Liang, Li; Olar, Adriana; Niu, Na; Jiang, Yi; Cheng, Wenjun; Bian, Xiu-Wu; Yang, Wentao; Zhang, Jing; Yemelyanova, Anna; Malpica, Anais; Zhang, Zhihong; Fuller, Gregory N; Liu, Jinsong

    2016-06-01

    Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1-R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were

  13. Dynamic changes of glial fibrillary acidic protein and nestin in the hippocampus of adult rat brain following ischemic vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Tianping Yu; Peng Zhang; Xiong Zhang; Linhui Wang; Mingyuan Tian; Yu Li

    2011-01-01

    Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days (P<0.01). The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.

  14. A transient wave of BMP signaling in the retina is necessary for Müller glial differentiation.

    Science.gov (United States)

    Ueki, Yumi; Wilken, Matthew S; Cox, Kristen E; Chipman, Laura B; Bermingham-McDonogh, Olivia; Reh, Thomas A

    2015-02-01

    The primary glial cells in the retina, the Müller glia, differentiate from retinal progenitors in the first postnatal week. CNTF/LIF/STAT3 signaling has been shown to promote their differentiation; however, another key glial differentiation signal, BMP, has not been examined during this period of Müller glial differentiation. In the course of our analysis of the BMP signaling pathway, we observed a transient wave of Smad1/5/8 signaling in the inner nuclear layer at the end of the first postnatal week, from postnatal day (P) 5 to P9, after the end of neurogenesis. To determine the function of this transient wave, we blocked BMP signaling during this period in vitro or in vivo, using either a BMP receptor antagonist or noggin (Nog). Either treatment leads to a reduction in expression of the Müller glia-specific genes Rlbp1 and Glul, and the failure of many of the Müller glia to repress the bipolar/photoreceptor gene Otx2. These changes in normal Müller glial differentiation result in permanent disruption of the retina, including defects in the outer limiting membrane, rosette formation and a reduction in functional acuity. Our results thus show that Müller glia require a transient BMP signal at the end of neurogenesis to fully repress the neural gene expression program and to promote glial gene expression. PMID:25605781

  15. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

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    Mami eNoda

    2015-06-01

    Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

  16. Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours

    International Nuclear Information System (INIS)

    Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B-mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery

  17. Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus

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    Miller Janet M

    2010-05-01

    Full Text Available Abstract Background Reactive astrocytosis and microgliosis are important features of the pathophysiology of hydrocephalus, and persistent glial "scars" that form could exacerbate neuroinflammation, impair cerebral perfusion, impede neuronal regeneration, and alter biomechanical properties. The purpose of this study was to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce gliosis in the H-Tx rat model of congenital hydrocephalus. Methods Minocycline (45 mg/kg/day i.p. in 5% sucrose at a concentration of 5-10 mg/ml was administered to hydrocephalic H-Tx rats from postnatal day 15 to day 21, when ventriculomegaly had reached moderate to severe stages. Treated animals were compared to age-matched non-hydrocephalic and untreated hydrocephalic littermates. The cerebral cortex (both gray matter laminae and white matter was processed for immunohistochemistry (glial fibrillary acidic protein, GFAP, for astrocytes and ionized calcium binding adaptor molecule, Iba-1, for microglia and analyzed by qualitative and quantitative light microscopy. Results The mean number of GFAP-immunoreactive astrocytes was significantly higher in untreated hydrocephalic animals compared to both types of controls (p p p Conclusions Overall, these data suggest that minocycline treatment is effective in reducing the gliosis that accompanies hydrocephalus, and thus may provide an added benefit when used as a supplement to ventricular shunting.

  18. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

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    Corinne Beurrier

    Full Text Available Ciliary neurotrophic factor (CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA was significantly reduced (by approximately 75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs, whose recovery was significantly higher in CNTF rats compared to controls (approximately 40% vs. approximately 7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (gamma-D-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.

  19. Agenesis of the Corpus Callosum Due to Defective Glial Wedge Formation in Lhx2 Mutant Mice.

    Science.gov (United States)

    Chinn, Gregory A; Hirokawa, Karla E; Chuang, Tony M; Urbina, Cecilia; Patel, Fenil; Fong, Jeanette; Funatsu, Nobuo; Monuki, Edwin S

    2015-09-01

    Establishment of the corpus callosum involves coordination between callosal projection neurons and multiple midline structures, including the glial wedge (GW) rostrally and hippocampal commissure caudally. GW defects have been associated with agenesis of the corpus callosum (ACC). Here we show that conditional Lhx2 inactivation in cortical radial glia using Emx1-Cre or Nestin-Cre drivers results in ACC. The ACC phenotype was characterized by aberrant ventrally projecting callosal axons rather than Probst bundles, and was 100% penetrant on 2 different mouse strain backgrounds. Lhx2 inactivation in postmitotic cortical neurons using Nex-Cre mice did not result in ACC, suggesting that the mutant phenotype was not autonomous to the callosal projection neurons. Instead, ACC was associated with an absent hippocampal commissure and a markedly reduced to absent GW. Expression studies demonstrated strong Lhx2 expression in the normal GW and in its radial glial progenitors, with absence of Lhx2 resulting in normal Emx1 and Sox2 expression, but premature exit from the cell cycle based on EdU-Ki67 double labeling. These studies define essential roles for Lhx2 in GW, hippocampal commissure, and corpus callosum formation, and suggest that defects in radial GW progenitors can give rise to ACC. PMID:24781987

  20. Nogo receptor 1 is expressed in both primary cultured glial cells and neurons

    Science.gov (United States)

    Ukai, Junichi; Imagama, Shiro; Ohgomori, Tomohiro; Ito, Zenya; Ando, Kei; Ishiguro, Naoki; Kadomatsu, Kenji

    2016-01-01

    ABSTRACT Nogo receptor (NgR) is common in myelin-derived molecules, i.e., Nogo, MAG, and OMgp, and plays important roles in both axon fasciculation and the inhibition of axonal regeneration. In contrast to NgR’s roles in neurons, its roles in glial cells have been poorly explored. Here, we found a dynamic regulation of NgR1 expression during development and neuronal injury. NgR1 mRNA was consistently expressed in the brain from embryonic day 18 to postnatal day 25. In contrast, its expression significantly decreased in the spinal cord during development. Primary cultured neurons, microglia, and astrocytes expressed NgR1. Interestingly, a contusion injury in the spinal cord led to elevated NgR1 mRNA expression at the injury site, but not in the motor cortex, 14 days after injury. Consistent with this, astrocyte activation by TGFβ1 increased NgR1 expression, while microglia activation rather decreased NgR1 expression. These results collectively suggest that NgR1 expression is enhanced in a milieu of neural injury. Our findings may provide insight into the roles of NgR1 in glial cells.

  1. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

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    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  2. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders.

    Science.gov (United States)

    Noda, Mami

    2015-01-01

    It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS). Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of the human brain, leading to various neurological dysfunctions. In the adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Although impact of hypothyroidism on synaptic transmission and plasticity is known, its effect on glial cells and related cellular mechanisms remain enigmatic. This mini-review article summarizes how THs are transported into the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, demonstrating an example of glioendocrine system. Neuroglial effects may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders. PMID:26089777

  3. Effects of X-irradiation on glial cells in the developing rat brain

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    Ferrer, I.; Borras, D. (Barcelona Univ. (Spain) Hospitalet de Llobregat. Unidad Neuropatologia)

    1994-08-01

    Sprague-Dawley rats were given a single dose of 2Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6h after irradiation; dead cells were cleared 48h later. These effects were almost abolished with the injection of cyclohexamide (1 [mu]g/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G[sub 1] and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-[alpha] (transformerly growth factor) antibodies that are used as putative oligodendrogial cell markers in the white matter of rat. (author).

  4. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

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    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  5. Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation

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    Gokhan Solen

    2010-02-01

    Full Text Available Abstract Background Long non-protein-coding RNAs (ncRNAs are emerging as important regulators of cellular differentiation and are widely expressed in the brain. Results Here we show that many long ncRNAs exhibit dynamic expression patterns during neuronal and oligodendrocyte (OL lineage specification, neuronal-glial fate transitions, and progressive stages of OL lineage elaboration including myelination. Consideration of the genomic context of these dynamically regulated ncRNAs showed they were part of complex transcriptional loci that encompass key neural developmental protein-coding genes, with which they exhibit concordant expression profiles as indicated by both microarray and in situ hybridization analyses. These included ncRNAs associated with differentiation-specific nuclear subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental enhancers and genes encoding important transcription factors and homeotic proteins. We also observed changes in ncRNA expression profiles in response to treatment with trichostatin A, a histone deacetylase inhibitor that prevents the progression of OL progenitors into post-mitotic OLs by altering lineage-specific gene expression programs. Conclusion This is the first report of long ncRNA expression in neuronal and glial cell differentiation and of the modulation of ncRNA expression by modification of chromatin architecture. These observations explicitly link ncRNA dynamics to neural stem cell fate decisions, specification and epigenetic reprogramming and may have important implications for understanding and treating neuropsychiatric diseases.

  6. Titanium dioxide nanoparticles inhibit proliferation and induce morphological changes and apoptosis in glial cells

    International Nuclear Information System (INIS)

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and be deposited in the hippocampus region. We determined the effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated proliferation by crystal violet staining, internalization of TiO2 NPs, and cellular morphology by TEM analysis, as well as F-actin distribution by immunostaining and cell death by detecting active caspase-3 and DNA fragmentation. TiO2 NPs inhibited proliferation and induced morphological changes that were related with a decrease in immuno-location of F-actin fibers. TiO2 NPs were internalized and formation of vesicles was observed. TiO2 NPs induced apoptosis after 96 h of treatment. Hence, TiO2 NPs had a cytotoxic effect on glial cells, suggesting that exposure to TiO2 NPs could cause brain injury and be hazardous to health.

  7. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  8. Glial response to 17β-estradiol in neonatal rats with excitotoxic brain injury.

    Science.gov (United States)

    Pansiot, Julien; Pham, Hoa; Dalous, Jeremie; Chevenne, Didier; Colella, Marina; Schwendimann, Leslie; Fafouri, Assia; Mairesse, Jérôme; Moretti, Raffaella; Schang, Anne-Laure; Charriaut-Marlangue, Christiane; Gressens, Pierre; Baud, Olivier

    2016-08-01

    White-matter injury is the most common cause of the adverse neurodevelopmental outcomes observed in preterm infants. Only few options exist to prevent perinatal brain injury associated to preterm delivery. 17β-estradiol (E2) is the predominant estrogen in circulation and has been shown to be neuroprotective in vitro and in vivo. However, while E2 has been found to modulate inflammation in adult models of brain damage, how estrogens influence glial cells response in the developing brain needs further investigations. Using a model of ibotenate-induced brain injury, we have refined the effects of E2 in the developing brain. E2 provides significant neuroprotection both in the cortical plate and the white matter in neonatal rats subjected to excitotoxic insult mimicking white matter and cortical damages frequently observed in very preterm infants. E2 promotes significant changes in microglial phenotypes balance in response to brain injury and the acceleration of oligodendrocyte maturation. Maturational effects of E2 on myelination process were observed both in vivo and in vitro. Altogether, these data demonstrate that response of glial cells to E2 could be responsible for its neuroprotective properties in neonatal excitotoxic brain injury. PMID:27222132

  9. Role of spinal glial cells in bee-toxin-induced spontaneous pain, hyperalgesia, and inflammation

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    Yao LU

    2012-08-01

    Full Text Available Objective To observe the effects of intrathecal injection of fluorocitrate, a glial metabolism inhibitor, on bee-toxin-induced spontaneous pain, hyperalgesia and inflammatory response. Methods Forty adult male SD rats with intrathecal catheterization were randomly divided into five groups (8 each: (1 bee-toxin alone group; (2 vehicle (solvent group; (3 low dose (1nmol fluorocitrate group; (4 middle dose (10nmol fluorocitrate group; (5 high dose (50nmol fluorocitrate group. After the measurement of rat paw withdrawal mechanical threshold (PWMT and paw volume (PV, the drug or vehicle was administered intrathecally. Twenty minutes later, bee-toxin (0.2mg/50μl was intraplantarly injected into the left hind paw of every rat, and spontaneous flinching reflexes (SFR were observed instantly for 1 hour. Two hours later, PWMT and PV were measured again. Results Intraplantar injection of bee-toxin into one hind paw of rat induced persistent SFR lasting for 1 hour, with PWMT decreased and PV increased in the injected paw. Compared with control group, pretreatment with intrathecal injection of fluorocitrate produced a significant inhibition of bee-toxin-induced persistent SFR (P < 0.05, P < 0.01, decreased the PWMT in a dose-dependent manner (P < 0.05, but it had no effect on bee-toxin-induced paw edema. Conclusion Activation of spinal glial cells may participate in bee-toxin-induced spontaneous pain and mechanical hyperalgesia, but not inflammatory response.

  10. Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism

    Science.gov (United States)

    López-Hernández, Tania; Ridder, Margreet C.; Montolio, Marisol; Capdevila-Nortes, Xavier; Polder, Emiel; Sirisi, Sònia; Duarri, Anna; Schulte, Uwe; Fakler, Bernd; Nunes, Virginia; Scheper, Gert C.; Martínez, Albert; Estévez, Raúl; van der Knaap, Marjo S.

    2011-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed that some patients without MLC1 mutations display the classical phenotype; others improve or become normal but retain macrocephaly. To find another MLC-related gene, we used quantitative proteomic analysis of affinity-purified MLC1 as an alternative approach and found that GlialCAM, an IgG-like cell adhesion molecule that is also called HepaCAM and is encoded by HEPACAM, is a direct MLC1-binding partner. Analysis of 40 MLC patients without MLC1 mutations revealed multiple different HEPACAM mutations. Ten patients with the classical, deteriorating phenotype had two mutations, and 18 patients with the improving phenotype had one mutation. Most parents with a single mutation had macrocephaly, indicating dominant inheritance. In some families with dominant HEPACAM mutations, the clinical picture and magnetic resonance imaging normalized, indicating that HEPACAM mutations can cause benign familial macrocephaly. In other families with dominant HEPACAM mutations, patients had macrocephaly and mental retardation with or without autism. Further experiments demonstrated that GlialCAM and MLC1 both localize in axons and colocalize in junctions between astrocytes. GlialCAM is additionally located in myelin. Mutant GlialCAM disrupts the localization of MLC1-GlialCAM complexes in astrocytic junctions in a manner reflecting the mode of inheritance. In conclusion, GlialCAM is required for proper localization of MLC1. HEPACAM is the second gene found to be mutated in MLC. Dominant HEPACAM mutations can cause either macrocephaly and mental retardation with or without autism or benign familial macrocephaly. PMID:21419380

  11. Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.

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    Min Du

    Full Text Available The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.

  12. Effect of the control proliferation of astrocyte on the formation of glial scars by antisense GFAP retrovirus

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Astrocytes play an important role in the formation of glial scars.In order to investigate the effect of inhibiting GFAP gene expression on normal,reactive astrocytes and on glial scar formation,the efficiency of the recombinant antisense GFAP retrovirus (PLBskG) on the growth,cell cycle,morphology and GFAP gene expression of astrocytes in vitro and on the formation of glial scars in vivo has been studied by cell growth curves,flow cytometry,immunocytochemistry,in situ hybridization,RT-PCR and Southern blot.The results confirm the recombinant retrovirus (PLBskG) produced growth suppression and G1 arrest of the normal and injured astrocytes.The infected cells become round or ellipoid.The cell processes become fine or retracted.The intensity of staining of GFAP is reduced.Expression of GFAP mRNA is down regulated.However,in the control experiment,no obvious effects on the morphology or synthesis of GFAP on cultured normal and scratched astrocytes infected by primary retrovirus vector (PLXSN) have been observed.The supernatant of PLBskG has been injected into an injured site by microinjection in vivo.The number and process lengths of GFAP positive cells are obviously reduced around the injured site.The formation of the glial scar is inhibited,showing that the recombinant antisense GFAP retrovirus can effectively inhibit the growth and GFAP expression of normal and injured astrocytes in vitro and the formation of glial scar in vivo.It is suggested that GFAP plays an important role in glial scar formation.

  13. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2012-02-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  14. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2011-01-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  15. Magnetic resonance diffusion and perfusion for differentiation and grading the diffuse glial brain tumors

    International Nuclear Information System (INIS)

    Full text: The aim is to investigate the role and importance of diffusion and perfusion magnetic resonance techniques in the diagnosis, differentiation and grading of diffuse glial brain tumors, and to determine whether there is a statistically significant difference in ADC and rCBV values of different types of gliomas according to their histopathologic grade and to calculate thresholds values for distinguishing high- from low-gradeglioma. Standard protocol, including SAG T1, AX T2, AX T2 FlAIR, COR T2 FlAIR, 3D T1 + C, in combination with diffusion and perfusion sequences. 46 patients with glial tumors, histologically verified are included. Grade distribution in three groups: II gr WHO-11 in number; III gr WHO-9; IV gr WHO- 26 in number. Calculation of the minimum value of the ADC and the maximum value of rCBV for each glioma. To understand the relationship between the minimum and maximum values of ADC rCBV and tumor grade were analyzed values in the three groups by the Mann-Whitney U test. Make a ROC (receiver operating characteristic) analysis to determine the optimal thresholds minADC, maxrCBV for tumor grading (with the best combination of sensitivity and specificity for differentiating WHO IIgr low-grade from III, IV gr WHO highgrade glioma. There were statistically significant differences in values of rCBVmax ADCmin between glial tumors II gr and III gr, II gr and IV gr but not III gr and IV gr WHO. The threshold values of ADC and rCBV for differentiation of low from high-grade glioma, were respectively: ADC = 1,1x10-3 mm2 / sec (with 91.1% accuracy, sensitivity 97.06%, specificity 72,73%; PPV 91,67%; NPV 88,89%); rCBV = 1,6 (with 91.11% accuracy, sensitivity 100%, specificity 63,64%; PPV 89,47%; NPV 100%). Functional MR sequences such as diffusion and perfusion can provide important additional information and improve glioma grading

  16. Glial cell activity is maintained during prolonged inflammatory challenge in rats

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    B.C. Borges

    2012-08-01

    Full Text Available We evaluated the expression of glial fibrillary acidic protein (GFAP, glutamine synthetase (GS, ionized calcium binding adaptor protein-1 (Iba-1, and ferritin in rats after single or repeated lipopolysaccharide (LPS treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g received ip injections of LPS (100 µg/kg or saline for 6 days: 6 saline (N = 5, 5 saline + 1 LPS (N = 6 and 6 LPS (N = 6. After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5 and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5, and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1. We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9. Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9 or repeated (47.6 ± 1.1 vs 28.1 ± 1.9 LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2 and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1, but had no effect in the retrochiasmatic nucleus (RCA and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1. The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  17. Glial cell activity is maintained during prolonged inflammatory challenge in rats

    Energy Technology Data Exchange (ETDEWEB)

    Borges, B.C.; Rorato, R.; Antunes-Rodrigues, J.; Elias, L.L.K. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP (Brazil)

    2012-05-04

    We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  18. Usefulness of short TE proton MR spectroscopy in grading brain glial tumors

    International Nuclear Information System (INIS)

    To determine the usefulness of in-vivo proton MR spectroscopy (MRS) with short TE for grading glial brain tumors. For the purpose of tumor grading, 32 patients with pathologically confirmed glial tumors were examined by proton MRS. This and MRI were performed on a 1.5T superconductive MR scanner. T2-weighted FSE images (TR/TE=3D4000/100 msec) were used to obtain anatomical reference images. The stimulated-echo acquisition mode (STEAM:TR/TE/MT=3D3000/30/13.7 msec) was used to acquire MRS data from the localized single-voxel (2x2x2 cm3) in both hemispheres. Residual water resonance in the spectra was removed using a CHESS pulse sequence. Prior to baseline correction, MRS raw-data, free induction decay signals were zero-filled, apodized by an exponential function with 8 Hz line-broadening, and fourier transformed. To normalize signal intensities of metabolites such as N-acetyl aspartate (NAA), total chloline (Cho), myo-inositol ml), and lactate (Lac), the creatine (Cr) peak was used as a standard. The concentration ratios of Cho/Cr, mI/Cr, α-Glx, Lac, and NAA/Cr changed lineaarly according to tumor grade. Increased Cho, mI, αGIx, and Lac levels were clearly seen in all grades. The most dramatic increases, observed in either Grade III or IV, were 78% and 228% for Cho (p less than 0.001), 106% and 61% for mI (p less than 0.001), 32% and 5% for α-Glx, and 727% and 450% for Lac (p less than 0.001), respectively. Increase of concentration ratio of Lac/Cr observed only in Grade III and Grade IV. The concentration ratios of NAA/Cr decreased gradually as tumor grade increased (p less than 0.001). The metabolic changes seen on proton MR spectroscopy using short TE might be useful for grading glial brain tumors. (author)

  19. The Proteome of Native Adult Müller Glial Cells From Murine Retina.

    Science.gov (United States)

    Grosche, Antje; Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca; von Toerne, Christine; Merl-Pham, Juliane; Hauck, Stefanie M

    2016-02-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  20. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

    Science.gov (United States)

    Gomes, Felipe V; Llorente, Ricardo; Del Bel, Elaine A; Viveros, Maria-Paz; López-Gallardo, Meritxell; Guimarães, Francisco S

    2015-05-01

    NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal

  1. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

    Directory of Open Access Journals (Sweden)

    Nedelkoska Liljana

    2007-12-01

    Full Text Available Abstract Background In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells. Methods To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M on CNS glia after 6 hours of treatment. Results In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells. Conclusion Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system.

  2. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J; Verwer, R W H; van Wamelen, D J; Qi, X-R; Gao, S-F; Lucassen, P J; Swaab, D F

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neu

  3. QUANTIFICATION OF GLIAL FIBRILLARY ACIDIC PROTEIN: COMPARISON OF SLOT-IMMUNOBINDING ASSAYS WITH A NOVEL SANDWICH ELISA

    Science.gov (United States)

    Detailed protocols are presented for assaying glial fibrillary acidic protein (GFAP), an astrocyte localized protein rich serves as a quantitative marker of toxicant- induced injury to the central nervous system. wo different solid-phase assay procedures are described: 1) a nitro...

  4. The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Sagar Devi

    2011-11-01

    Full Text Available Abstract Background Clinical studies of osteoarthritis (OA suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia was assessed. Spinal cord microglia (Iba1 staining and astrocyte (GFAP immunofluorescence activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. Results Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p Conclusions Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

  5. A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC.

    Science.gov (United States)

    Singhvi, Aakanksha; Liu, Bingqian; Friedman, Christine J; Fong, Jennifer; Lu, Yun; Huang, Xin-Yun; Shaham, Shai

    2016-05-01

    Neurons receive input from the outside world or from other neurons through neuronal receptive endings (NREs). Glia envelop NREs to create specialized microenvironments; however, glial functions at these sites are poorly understood. Here, we report a molecular mechanism by which glia control NRE shape and associated animal behavior. The C. elegans AMsh glial cell ensheathes the NREs of 12 neurons, including the thermosensory neuron AFD. KCC-3, a K/Cl transporter, localizes specifically to a glial microdomain surrounding AFD receptive ending microvilli, where it regulates K(+) and Cl(-) levels. We find that Cl(-) ions function as direct inhibitors of an NRE-localized receptor-guanylyl-cyclase, GCY-8, which synthesizes cyclic guanosine monophosphate (cGMP). High cGMP mediates the effects of glial KCC-3 on AFD shape by antagonizing the actin regulator WSP-1/NWASP. Components of this pathway are broadly expressed throughout the nervous system, suggesting that ionic regulation of the NRE microenvironment may be a conserved mechanism by which glia control neuron shape and function. PMID:27062922

  6. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    NARCIS (Netherlands)

    Warringa, R.A.J.; Hoeben, R.C.; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated

  7. Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction

    DEFF Research Database (Denmark)

    Teglbjærg, Lars Stubbe; Hansen, J-ES; Dalbøge, H;

    1991-01-01

    This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot hybrid...... where viral replication is absent, or where genomic copies are present at such low numbers that they are otherwise undetectable....

  8. Sonographic nomogram of the leptomeninges (pia-glial plate) and its usefulness for evaluating bacterial meningitis in infants

    OpenAIRE

    Jequier, Sigrid; Jéquier, J C

    1999-01-01

    To our knowledge, the upper limits of the thickness of normal meninges on neurosonograms are not known. We therefore established a nomogram for sonographic measurements of the leptomeninges (pia-glial plate) and assessed its usefulness in neurosonographic examinations of children with bacterial meningitis.

  9. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

    Directory of Open Access Journals (Sweden)

    Pavel Nikolaevich Vlasov

    2009-12-01

    This investigation was undertaken to study the implication of the DV phenomenon in the clinical picture of glial brain tumors (GBT. One hundred and sixty-one subjects (mean age 29,2±6,4 years; males 47%, including 129 healthy individuals and 32 patients with GBT, were examined. In the clinical picture of GBT with seizures, DV is a common symptom that is encountered in the involvement of predominantly the right temporal lobe and accompanied by generalized convulsive attacks and olfactory hallucinations. DV in GBT occurs more than once daily; its duration is a few (as many as 5 minutes; DV is characterized by a negative emotional tinge and attended by fear

  10. In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells.

    Science.gov (United States)

    Li, Hedong; Chen, Gong

    2016-08-17

    Neuroregeneration in the CNS has proven to be difficult despite decades of research. The old dogma that CNS neurons cannot be regenerated in the adult mammalian brain has been overturned; however, endogenous adult neurogenesis appears to be insufficient for brain repair. Stem cell therapy once held promise for generating large quantities of neurons in the CNS, but immunorejection and long-term functional integration remain major hurdles. In this Perspective, we discuss the use of in vivo reprogramming as an emerging technology to regenerate functional neurons from endogenous glial cells inside the brain and spinal cord. Besides the CNS, in vivo reprogramming has been demonstrated successfully in the pancreas, heart, and liver and may be adopted in other organs. Although challenges remain for translating this technology into clinical therapies, we anticipate that in vivo reprogramming may revolutionize regenerative medicine by using a patient's own internal cells for tissue repair. PMID:27537482

  11. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

    Science.gov (United States)

    Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.

    2001-11-01

    Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

  12. Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity

    Institute of Scientific and Technical Information of China (English)

    Sacha A. Malin; Brian M. Davis

    2008-01-01

    The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family,which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV 1, to produce long-lasting hyperalgesia.

  13. Immunohistochemical visualization of neurons and specific glial cells for stereological application in the porcine neocortex

    DEFF Research Database (Denmark)

    Lyck, Lise; Jelsing, Jacob; Jensen, Pia Søndergaard;

    2006-01-01

    The pig is becoming an increasingly used non-primate model in basic experimental studies of human neurological diseases. In spite of the widespread use of immunohistochemistry and cell type specific markers, the application of immunohistochemistry in the pig brain has not been systematically...... described. Therefore, to facilitate future stereological studies of the neuronal and glial cell populations in experimental neurological diseases in the pig, we established a battery of immunohistochemical protocols for staining of perfusion fixed porcine brain tissue processed as free floating cryostat......-, vibratome- or paraffin sections. Antibodies against NeuN, GFAP, S100-protein, MBP, CNPase, CD11b, CD68 (KP1), CD45 and Ki67 were evaluated, and all except CD68 and CD45 resulted in staining of high quality in either type of tissue. Each staining was evaluated with respect to specificity and sensitivity in...

  14. Glial cell line-derived neurotrophic factor (GDNF therapy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Shingo,Tetsuro

    2007-04-01

    Full Text Available Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD, although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.

  15. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    DEFF Research Database (Denmark)

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa;

    2014-01-01

    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was...... chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These...

  16. Glial cells of the central nervous system of Bothrops jararaca (Reptilia, Ofidae: an ultrastructural study

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    Eduardo F. Bondan

    2015-07-01

    Full Text Available Abstract Although ultrastructural characteristics of mature neuroglia in the central nervous system (CNS are very well described in mammals, much less is known in reptiles, especially serpents. In this context, two specimens of Bothrops jararaca were euthanized for morphological analysis of CNS glial cells. Samples from telencephalon, mesencephalon and spinal cord were collected and processed for light and transmission electron microscopy investigation. Astrocytes, oligodendrocytes, microglial cells and ependymal cells, as well as myelin sheaths, presented similar ultrastructural features to those already observed in mammals and tended to maintain their general aspect all over the distinct CNS regions observed. Morphological similarities between reptilian and mammalian glia are probably linked to their evolutionary conservation throughout vertebrate phylogeny.

  17. Phenotype overlap in glial cell populations: astroglia, oligodendroglia and NG-2(+ cells

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    Robert eFern

    2015-05-01

    Full Text Available The extent to which NG-2(+ cells form a distinct population separate from astrocytes is central to understanding whether this important cell class is wholly an oligodendrocyte precursor cell (OPC or has additional functions akin to those classically ascribed to astrocytes. Early immuno-staining studies indicate that NG-2(+ cells do not express the astrocyte marker GFAP, but orthogonal reconstructions of double-labelled confocal image stacks here reveal a significant degree of co-expression in individual cells within post-natal day 10 (P10 rat optic nerve (RON and rat cortex. Extensive scanning of various antibody/fixation/embedding approaches identified a protocol for selective post-embedded immuno-gold labelling. This first ultrastructural characterization of identified NG-2(+ cells revealed populations of both OPCs and astrocytes in P10 RON. NG-2(+ astrocytes had classic features including the presence of glial filaments but low levels of glial filament expression were also found in OPCs and myelinating oligodendrocytes. P0 RONs contained few OPCs but positively identified astrocytes were observed to ensheath pre-myelinated axons in a fashion previously described as a definitive marker of the oligodendrocyte lineage. Astrocyte ensheathment was also apparent in P10 RONs, was absent from developing nodes of Ranvier and was never associated with compact myelin. Astrocyte processes were also shown to encapsulate some oligodendrocyte somata. The data indicate that common criteria for delineating astrocytes and oligodendroglia are insufficiently robust and that astrocyte features ascribed to OPCs are likely to arise from misidentification.

  18. Prolonged minocycline treatment impairs motor neuronal survival and glial function in organotypic rat spinal cord cultures.

    Directory of Open Access Journals (Sweden)

    Josephine Pinkernelle

    Full Text Available BACKGROUND: Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer's disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. METHODS: In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM at various time points in culture and fixed after 1 week. RESULTS: Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. CONCLUSIONS: The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients.

  19. Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

    International Nuclear Information System (INIS)

    Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

  20. Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism.

    Science.gov (United States)

    Derouiche, Amin; Haseleu, Julia; Korf, Horst-Werner

    2015-12-01

    The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism. PMID:25894677

  1. Inhibitory effect of synthetic small interfering RNAs on glial fibrillary acidic expression in astrocytes

    Institute of Scientific and Technical Information of China (English)

    Mingzhu Zhang; Qing Zhao; Xin Tang; Guangrong Yu

    2008-01-01

    BACKGROUND: Glial fibrillary acidic protein (GFAP) expression highly correlates with spinal glial scar formation, and is regarded as an important target for scar therapy. Efficient inhibition of expression could benefit recovery from spinal cord injury. OBJECTIVE: To investigate the inhibitory effects of synthetic small interfering RNAs (siRNAs) on astrocytie GFAP expression in rats. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment at the cellular and molecular level was performed at the First Hospital of Dalian Medical University between June 2005 and February 2006. MATERIALS: A total of 100 seven-day-old, Sprague Dawley rats were selected. GAPDH siRNA was purchased from Ambion, USA, And TransMessengerTM Transfection Reagent from DAKO, Carpinteria, CA. METHODS: Rat astrocytes were isolated and cultured. Three pairs of 21-nucleotide (nt) siRNAs specific to rats GFAP mRNA, 401,404 and 854, were synthesized and transfected in primary astrocytes at 1, 2, 3, and 4 g/L using TransMessengerTM Transfection Reagent. Non-transfected astrocytes served as the blank group. Cells transfected with siRNA were regarded as the negative control group, with GAPDH siRNA as the positive control group, and 401 siRNA, 404 siRNA, and 854 siRNA as experimental groups. MAIN OUTCOME MEASURES: GFAP mRNA and protein expression were assessed by RT-PCR and Western blot, respectively, at 24, 48, and 72 hours of culture. RESULTS: GFAP mRNA expression in the positive control group was significantly less than the negative control group (P0.05). GFAP protein expression was remarkably less in siRNA-transfected astroeytes compared to the blank control (P < 0.01). CONCLUSION: Transfected siRNAs could significantly inhibit GFAP gene expression in astrocytes after 72 hours in culture.

  2. Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice.

    Science.gov (United States)

    Melendez, Roberto I; Roman, Cristina; Capo-Velez, Coral M; Lasalde-Dominicci, Jose A

    2016-06-01

    The mechanisms leading to the neurocognitive deficits in humans with immunodeficiency virus type 1 (HIV-1) are not well resolved. A number of cell culture models have demonstrated that the HIV-envelope glycoprotein 120 (gp120) decreases the reuptake of glutamate, which is necessary for learning, memory, and synaptic plasticity. However, the impact of brain HIV-1 gp120 on glutamate uptake systems in vivo remains unknown. Notably, alterations in brain glutamate uptake systems are implicated in a number of neurodegenerative and neurocognitive disorders. We characterized the kinetic properties of system XAG (sodium-dependent) and systems xc- (sodium-independent) [3H]-L-glutamate uptake in the striatum and hippocampus of HIV-1 gp120 transgenic mice, an established model of HIV neuropathology. We determined the kinetic constant Vmax (maximal velocity) and Km (affinity) of both systems XAG and xc- using subcellular preparations derived from neurons and glial cells. We show significant (30-35 %) reductions in the Vmax of systems XAG and xc- in both neuronal and glial preparations derived from the striatum, but not from the hippocampus of gp120 mice relative to wild-type (WT) controls. Moreover, immunoblot analysis showed that the protein expression of glutamate transporter subtype-1 (GLT-1), the predominant brain glutamate transporter, was significantly reduced in the striatum but not in the hippocampus of gp120 mice. These extensive and region-specific deficits of glutamate uptake likely contribute to the development and/or severity of HIV-associated neurocognitive disorders. Understanding the role of striatal glutamate uptake systems in HIV-1 gp120 may advance the development of new therapeutic strategies to prevent neuronal damage and improve cognitive function in HIV patients. PMID:26567011

  3. Double immunofluorescence shows coexpression of Bcl-x with GFAP in a variety of glial lesions.

    Science.gov (United States)

    Tan, Kong-Bing; Magdalene Koh, Hui-Keng; Tan, Soo-Yong

    2006-12-01

    Bcl-x is an important member of the bcl-2 family of proteins that has been shown to be expressed by both native nervous system tissue and several nervous system tumors. Its anti-apoptotic activity is believed to contribute to nervous system tumorigenesis. We seek to compare the staining characteristics of Bcl-x and GFAP in various neuronal and glial lesions, both neoplastic and non-neoplastic. We also use a double immunofluorescence technique to assess for coexpression of Bcl-x and GFAP by the same lesional cells. Forty cases of brain tumors and reactive brain conditions were reviewed. The former included astrocytomas, GBMs, ependymomas, oligodendrogliomas, gangliogliomas, subependymomas and neurocytomas. The latter included cases of gliosis, cerebritis and mesial temporal sclerosis. Immunohistochemistry for Bcl-x and GFAP was performed. Double immunofluorescent labeling using antibodies to both GFAP and Bcl-x was also carried out. Expression of Bcl-x closely follows that of GFAP with strong expression in both reactive astrocytes and astrocytomas. There is more focal expression in other gliomas. Immunostaining for Bcl-x is generally more intense and distinct, compared to that for GFAP. Expression of both GFAP and Bcl-x is more focal in oligodendrogliomas, with staining of mainly intervening astrocytic processes. Double immunolabelling confirms the coexpression of Bcl-x and GFAP in various gliomas and reactive brain conditions. As immunostaining for Bcl-x is generally more distinct and intense than that for GFAP, it may serve as a useful alternative to help highlight glial cells in selected diagnostic settings. PMID:16773221

  4. Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology and roles

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    Christian eGiaume

    2013-07-01

    Full Text Available Functional interaction between neurons and glia is an exciting field that has expanded tremendously during the past decade. Such partnership has multiple impacts on neuronal activity and survival. Indeed, numerous findings indicate that glial cells interact tightly with neurons in physiological as well as pathological situations. One typical feature of glial cells is their high expression level of gap junction protein subunits, named connexins (Cxs, thus the membrane channels they form may contribute to neuroglial interaction that impacts neuronal activity and survival. While the participation of gap junction channels in neuroglia interactions has been regularly reviewed in the past, the other channel function of Cxs, i.e. hemichannels located at the cell surface, has only recently received attention. While gap junction channels provide the basis for a unique direct cell-to-cell communication, Cx hemichannels allow the exchange of ions and signaling molecules between the cytoplasm and the extracellular medium, thus supporting autocrine and paracrine communication through a process referred to as gliotransmission, as well as uptake and release of metabolites. More recently, another family of proteins, termed pannexins (Panxs, has been identified. These proteins share similar membrane topology but no sequence homology with Cxs. They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels. Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs in glia. In the present review, we up-date and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglia interactions in healthy and diseased brain.

  5. Glial reaction in the hippocampus after global cardiogenic ischemia Reação glial no hipocampo após isquemia global cardiogênica

    Directory of Open Access Journals (Sweden)

    Emerson Fachin Martins

    2001-03-01

    Full Text Available Many experimental surgerical procedures have been perfomed in the analyse of the phenomenon of brain trophism and plasticity, however undesirable intercorrence can occour leading to specific changes in the results that should be taken into attention. To study this issue we have promoted a transient cardiogenic interruption of the blood flow together with a transient occlusion of the bilateral common carotid arteries (2VO in rats and analysed the state of activation of astrocyte and microglia by means of the glial fibrillary acidic protein (GFAP and OX42 immunohistochemistry, respectively. Rats were submitted to incomplete global cerebral ischemia (IGCI by occlusion of the bilateral carotid arteries for 30 minutes. During the IGCI surgical, some rats received a higher dose of the chloral hydrate anaesthesia which promoted a cardiogenic interruption of the blood flow (CIBF for a period of 10 minutes followed by and prompt reperfusion. During that period, animals were submited to a cardiac massage and ventilated. Sham operation were made in control animals. Rats were killed and their brains processed 14 days after the surgery. The animals that have received a IGCI showed a slight astroglial and microglial reaction in all subfields of the hippocampal formation, however the animal submitted to CIBF showed a massive infiltration of the reactive astrocyte and microglia in CA1 subfield. This results demonstrated that a transient occlusion of the bilateral common carotid arteries leads to activation of glial cells in the hippocampus, however this response can be remarkable changed in animal developing a transient systemic hypoperfusion during surgery. Thus, an accurated monitoration of the hemodinamic condition of the animal has to be done in experimental models of brain ischemia and the results have to be analysed in view of this aspect.Muitos procedimentos experimentais são desenvolvidos para analisar o fenômeno do trofismo e plasticidade cerebral

  6. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  7. Arginase 2 deletion reduces neuro-glial injury and improves retinal function in a model of retinopathy of prematurity.

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    Subhadra P Narayanan

    Full Text Available BACKGROUND: Retinopathy of prematurity (ROP is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2 in retinal neuro-glial cell injury in the mouse model of ROP. METHODS AND FINDINGS: Studies were performed using wild type (WT and A2 knockout (A2-/- mice exposed to Oxygen Induced Retinopathy (OIR. Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling and Western blotting. Electroretinography (ERG was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the mitochondrial protein Bim were markedly increased in WT OIR retinas compared to controls, whereas the pro-survival Mitochondrial protein BCL-xl was reduced. These alterations were largely blocked in the A2-/- OIR retina. CONCLUSIONS: Our data implicate A2 in neurodegeneration during ROP. Deletion of A2 significantly improves neuronal survival and function, possibly through the regulation of mitochondrial membrane permeability mediated apoptosis during retinal ischemia. These molecular events are associated with

  8. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

    Science.gov (United States)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  9. Serum Glial Fibrillary Acidic Protein Predicts Tissue Glial Fibrillary Acidic Protein Break-Down Products and Therapeutic Efficacy after Penetrating Ballistic-Like Brain Injury.

    Science.gov (United States)

    Boutté, Angela M; Deng-Bryant, Ying; Johnson, David; Tortella, Frank C; Dave, Jitendra R; Shear, Deborah A; Schmid, Kara E

    2016-01-01

    Acute traumatic brain injury (TBI) is associated with neurological dysfunction, changes in brain proteins, and increased serum biomarkers. However, the relationship between these brain proteins and serum biomarkers, and the ability of these serum biomarkers to indicate a neuroprotective/therapeutic response, remains elusive. Penetrating ballistic-like brain injury (PBBI) was used to systematically analyze several key TBI biomarkers, glial fibrillary acidic protein (GFAP) and its break-down products (BDPs)-ubiquitin C-terminal hydrolase-L1 (UCH-L1), α-II spectrin, and α-II spectrin BDPs (SBDPs)-in brain tissues and serum during an extended acute-subacute time-frame. In addition, neurological improvement and serum GFAP theranostic value was evaluated after neuroprotective treatment. In brain tissues, total GFAP increased more than three-fold 2 to 7 d after PBBI. However, this change was primarily due to GFAP-BDPs which increased to 2.7-4.8 arbitrary units (AU). Alpha-II spectrin was nearly ablated 3 d after PBBI, but somewhat recovered after 7 d. In conjunction with α-II spectrin loss, SBDP-145/150 increased approximately three-fold 2 to 7 d after PBBI (vs. sham, p<0.05). UCH-L1 protein levels were slightly decreased 7 d after PBBI but otherwise were unaffected. Serum GFAP was elevated by 3.2- to 8.8-fold at 2 to 4 h (vs. sham; p<0.05) and the 4 h increase was strongly correlated to 3 d GFAP-BDP abundance (r=0.66; p<0.05). Serum GFAP showed such a strong injury effect that it also was evaluated after therapeutic intervention with cyclosporin A (CsA). Administration of 2.5 mg/kg CsA significantly reduced serum GFAP elevation by 22.4-fold 2 h after PBBI (vs. PBBI+vehicle; p<0.05) and improved neurological function 1 d post-injury. Serum biomarkers, particularly GFAP, may be correlative tools of brain protein changes and feasible theranostic markers of TBI progression and recovery. PMID:25789543

  10. Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube.

    Science.gov (United States)

    Johnson, Kimberly; Moriarty, Chelsea; Tania, Nessy; Ortman, Alissa; DiPietrantonio, Kristina; Edens, Brittany; Eisenman, Jean; Ok, Deborah; Krikorian, Sarah; Barragan, Jessica; Golé, Christophe; Barresi, Michael J F

    2014-03-01

    Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of

  11. Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

    Science.gov (United States)

    Perucho, Juan; Gómez, Ana; Muñoz, María Paz; de Yébenes, Justo García; Mena, María Ángeles; Casarejos, María José

    2016-07-01

    The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In

  12. Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier

    Directory of Open Access Journals (Sweden)

    Peng YS

    2014-06-01

    Full Text Available Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 3Department of Materials Engineering, Tatung University, Taipei, 4Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, 5Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan *Yu-Shiang Peng and Po-Liang Lai contributed equally to this work Abstract: Parkinson’s disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood–brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810. This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the

  13. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  14. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

    DEFF Research Database (Denmark)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn;

    2014-01-01

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat......Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The...... differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative...

  15. Label-free distinguishing between neurons and glial cells based on two-photon excited fluorescence signal of neuron perinuclear granules

    Science.gov (United States)

    Du, Huiping; Jiang, Liwei; Wang, Xingfu; Liu, Gaoqiang; Wang, Shu; Zheng, Liqin; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2016-08-01

    Neurons and glial cells are two critical cell types of brain tissue. Their accurate identification is important for the diagnosis of psychiatric disorders such as depression and schizophrenia. In this paper, distinguishing between neurons and glial cells by using the two-photon excited fluorescence (TPEF) signals of intracellular intrinsic sources was performed. TPEF microscopy combined with TUJ-1 and GFAP immunostaining and quantitative image analysis demonstrated that the perinuclear granules of neurons in the TPEF images of brain tissue and the primary cultured cortical cells were a unique characteristic of neurons compared to glial cells which can become a quantitative feature to distinguish neurons from glial cells. With the development of miniaturized TPEF microscope (‘two-photon fiberscopes’) imaging devices, TPEF microscopy can be developed into an effective diagnostic and monitoring tool for psychiatric disorders such as depression and schizophrenia.

  16. Effect of interleukin-1β on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function

    OpenAIRE

    Constandil, Luis; Hernández, Alejandro; Pelissier, Teresa; Arriagada, Osvaldo; Espinoza, Karla; Burgos, Hector; Laurido, Claudio

    2009-01-01

    Introduction Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1β is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1β to healthy animals induces hyperalgesia and allodynia and enhances wind-up activity in dorsal horn neurons. Methods To investigate the functional contribution of glial cells in the spinal cord n...

  17. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    OpenAIRE

    Ribeiro-Resende Victor; Carrier-Ruiz Alvaro; R Lemes Robertha M; Reis Ricardo A M; Mendez-Otero Rosalia

    2012-01-01

    Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that s...

  18. Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

    OpenAIRE

    Kalliopi Ioannidou; Anderson, Kurt I; David Strachan; Edgar, Julia M.; Barnett, Susan C.

    2012-01-01

    Background Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize th...

  19. Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain.

    Directory of Open Access Journals (Sweden)

    Hideaki Yamamoto

    Full Text Available Adherens junctions (AJs play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.

  20. Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor*

    OpenAIRE

    Liu, Zhong-Wei; Li, Wen-qiang; Wang, Jun-kui; Ma, Xian-cang; Liang, Chen; Liu, Peng; Chu, Zheng; Dang, Yong-hui

    2014-01-01

    This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and act...

  1. Neonatal Neural Progenitor Cells and Their Neuronal and Glial Cell Derivatives Are Fully Permissive for Human Cytomegalovirus Infection▿

    OpenAIRE

    Luo, Min Hua; Philip H. Schwartz; Fortunato, Elizabeth A.

    2008-01-01

    Congenital human cytomegalovirus (HCMV) infection causes central nervous system structural abnormalities and functional disorders, affecting both astroglia and neurons with a pathogenesis that is only marginally understood. To better understand HCMV's interactions with such clinically important cell types, we utilized neural progenitor cells (NPCs) derived from neonatal autopsy tissue, which can be differentiated down either glial or neuronal pathways. Studies were performed using two viral i...

  2. Reexpression of glial fibrillary acidic protein rescues the ability of astrocytoma cells to form processes in response to neurons

    OpenAIRE

    1994-01-01

    Astroglial cells play an important role in orchestrating the migration and positioning of neurons during central nervous system development. Primary astroglia, as well as astrocytoma cells will extend long stable processes when co-cultured with granule neurons. In order to determine the function of the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astroglia and astrocytoma cells, we suppressed the expression of GFAP by stable transfection of an anti- sense...

  3. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization.

    Science.gov (United States)

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2016-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. PMID:26235241

  4. MYELIN BASIC PROTEIN-PRIMED T CELLS INDUCE NEUROTROPHINS IN GLIAL CELLS VIA α5β3 INTEGRIN

    OpenAIRE

    Roy, Avik; Liu, Xiaojuan; Pahan, Kalipada

    2007-01-01

    Increasing the level of neurotrophins within the CNS may have therapeutic efficacy in patients with various neurological diseases. Earlier we have demonstrated that myelin basic protein (MBP)-primed T cells induce the expression of various proinflammatory molecules in glial cells via cell-to-cell contact. Here we describe that after Th2 polarization by gemfibrozil or other drugs, MBP-primed T cells induced the expression of neurotrophic molecules such as, brain-derived neurotrophic factor (BD...

  5. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    International Nuclear Information System (INIS)

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab

  6. Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites

    OpenAIRE

    Kozlenkov, Alexey; Roussos, Panos; Timashpolsky, Alisa; Barbu, Mihaela; Rudchenko, Sergei; Bibikova, Marina; Klotzle, Brandy; Byne, William; Lyddon, Rebecca; Di Narzo, Antonio Fabio; Hurd, Yasmin L.; Eugene V Koonin; Dracheva, Stella

    2013-01-01

    We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island–containing promot...

  7. The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis

    OpenAIRE

    Cannella, Barbara; Hoban, Carolyn J; Gao, Yan-Ling; Garcia-Arenas, Renee; Lawson, Deborah; Marchionni, Mark; Gwynne, David; Raine, Cedric S.

    1998-01-01

    Glial growth factor 2 (GGF2) is a neuronal signal that promotes the proliferation and survival of the oligodendrocyte, the myelinating cell of the central nervous system (CNS). The present study examined whether recombinant human GGF2 (rhGGF2) could effect clinical recovery and repair to damaged myelin in chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the mouse, a major animal model for the human demyelinating disease, multiple sclerosis. Mice with EAE were treated with ...

  8. Chronic psychosocial stress and citalopram modulate the expression of the glial proteins GFAP and NDRG2 in the hippocampus

    OpenAIRE

    Araya-Callís, Carolina; Hiemke, Christoph; Abumaria, Nashat; Flugge, Gabriele

    2012-01-01

    Rationale It has been suggested that there are causal relationships between alterations in brain glia and major depression. Objectives To investigate whether a depressive-like state induces changes in brain astrocytes, we used chronic social stress in male rats, an established preclinical model of depression. Expression of two astrocytic proteins, the intermediate filament component glial fibrillary acidic protein (GFAP) and the cytoplasmic protein N-myc downregulated gene 2 (NDRG2), was anal...

  9. Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial

    OpenAIRE

    Mohebbi, Niayesh; Khoshnevisan, Alireza; Naderi, Soheil; Abdollahzade, Sina; Salamzadeh, Jamshid; Javadi, Mohammadreza; Mojtahedzadeh, Mojtaba; GHOLAMI, KHEIROLLAH.

    2014-01-01

    Background Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomiz...

  10. First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression

    OpenAIRE

    Polyakova, Maryna; Sander, Christian; Arelin, Katrin; Lampe, Leonie; Luck, Tobias; Luppa, Melanie; Kratzsch, Jürgen; Hoffmann, Karl-Titus; Riedel-Heller, Steffi; Villringer, Arno; Schoenknecht, Peter; Schroeter, Matthias L.

    2015-01-01

    Minor depression is diagnosed when a patient suffers from 2 to 4 depressive symptoms for at least 2 weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressive episo...

  11. First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression

    OpenAIRE

    Maryna Polyakova; Tobias Luck; Juergen Kratzsch; Karl-Titus Hoffmann; Arno Villringer

    2015-01-01

    Minor depression is diagnosed when a patient suffers from two to four depressive symptoms for at least two weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressiv...

  12. Neural progenitor cells isolated from the subventricular zone present hemichannel activity and form functional gap junctions with glial cells

    Science.gov (United States)

    Talaverón, Rocío; Fernández, Paola; Escamilla, Rosalba; Pastor, Angel M.; Matarredona, Esperanza R.; Sáez, Juan C.

    2015-01-01

    The postnatal subventricular zone (SVZ) lining the walls of the lateral ventricles contains neural progenitor cells (NPCs) that generate new olfactory bulb interneurons. Communication via gap junctions between cells in the SVZ is involved in NPC proliferation and in neuroblast migration towards the olfactory bulb. SVZ NPCs can be expanded in vitro in the form of neurospheres that can be used for transplantation purposes after brain injury. We have previously reported that neurosphere-derived NPCs form heterocellular gap junctions with host glial cells when they are implanted after mechanical injury. To analyze functionality of NPC-glial cell gap junctions we performed dye coupling experiments in co-cultures of SVZ NPCs with astrocytes or microglia. Neurosphere-derived cells expressed mRNA for at least the hemichannel/gap junction channel proteins connexin 26 (Cx26), Cx43, Cx45 and pannexin 1 (Panx1). Dye coupling experiments revealed that gap junctional communication occurred among neurosphere cells (incidence of coupling: 100%). Moreover, hemichannel activity was also detected in neurosphere cells as evaluated in time-lapse measurements of ethidium bromide uptake. Heterocellular coupling between NPCs and glial cells was evidenced in co-cultures of neurospheres with astrocytes (incidence of coupling: 91.0 ± 4.7%) or with microglia (incidence of coupling: 71.9 ± 6.7%). Dye coupling in neurospheres and in co-cultures was inhibited by octanol, a gap junction blocker. Altogether, these results suggest the existence of functional hemichannels and gap junction channels in postnatal SVZ neurospheres. In addition, they demonstrate that SVZ-derived NPCs can establish functional gap junctions with astrocytes or microglia. Therefore, cell-cell communication via gap junctions and hemichannels with host glial cells might subserve a role in the functional integration of NPCs after implantation in the damaged brain. PMID:26528139

  13. Satellite glial cells can promote the extension of neuronal axons in vitro

    Institute of Scientific and Technical Information of China (English)

    Jiu-Hong Zhao; Yi-Di Huang; Xi-Nan Yi; Quan-Peng Zhang; Xian-Fang Zhang; Xu Dong; Gang Luo; Hai-Ying Zhang; Kun-Ju Wang; Mei-Li Lao

    2015-01-01

    Objective: To study the influence of satellite glial cells (SGCs) on the outgrowth of neuronal neurite and the role of Slit1 protein and the contact with neurons in this process, in vitro. Methods: Neurons culture and SGC-neuron co-culture were used as the cell models. The length of axons and dendrites were measured via immunofluorescence to observe the influence of SGCs on the outgrowth of neuronal neurite. The Slit1 protein was added into SGC-neuron co-culture model. The length of dendrites was measured via immunofluorescence at different point times. Result: The anatomical relationship between neurons and SGCs changed as culture period expand. At 12 h after culture, SGCs all surrounded neurons; by 72 h after culture, SGCs were all off neurons. SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; when SGCs closely contact with neurons, the effect of Slit1 on promoting the dendritic growth is not obvious, but when SGCs were off neurons, the effect of Slit1 on promoting the dendritic growth is significant. Conclusion: SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; Slit- Robo signaling pathways and contact with neurons play a role in this process.

  14. Molecular cloning and primary structure of human glial fibrillary acidic protein

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, S.A.; Helman, L.J.; Allison, A.; Israel, M.A. (National Cancer Institute, Bethesda, MD (USA))

    1989-07-01

    Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in astroglia. Therefore, the authors isolated a cDNA clone encoding this protein and determined its nucleotide sequence. The predicted amino acid sequence indicates that GFAP shares structural similarities-particularly in the central rod domain and to a lesser degree in the carboxyl-terminal domain-with other IF proteins found in nonepithelial cell types. Considerable sequence divergence in the amino-terminal region of GFAP suggests that the tissue-specific functions of this IF protein might be mediated through this region of the molecule. In contrast, conservation of structural characteristics and a moderate degree of sequence conservation in the carboxyl-terminal region suggest functional similarities. Blot hybridization analysis using the GFAP cDNA as a probe failed to detect GFAP mRNA in both normal and neoplastic human tissues in which IF proteins other than GFAP are known to be expressed.

  15. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Nedeljković Nadežda

    2012-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

  16. High Resolution Dissection of Reactive Glial Nets in Alzheimer’s Disease

    Science.gov (United States)

    Bouvier, David S.; Jones, Emma V.; Quesseveur, Gaël; Davoli, Maria Antonietta; A. Ferreira, Tiago; Quirion, Rémi; Mechawar, Naguib; Murai, Keith K.

    2016-01-01

    Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research. PMID:27090093

  17. A model of space-fractional-order diffusion in the glial scar.

    Science.gov (United States)

    Prodanov, Dimiter; Delbeke, Jean

    2016-08-21

    Implantation of neuroprosthetic electrodes induces a stereotypical state of neuroinflammation, which is thought to be detrimental for the neurons surrounding the electrode. Mechanisms of this type of neuroinflammation are still poorly understood. Recent experimental and theoretical results point to a possible role of the diffusing species in this process. The paper considers a model of anomalous diffusion occurring in the glial scar around a chronic implant in two simple geometries - a separable rectilinear electrode and a cylindrical electrode, which are solvable exactly. We describe a hypothetical extended source of diffusing species and study its concentration profile in steady-state conditions. Diffusion transport is assumed to obey a fractional-order Fick law, derivable from physically realistic assumptions using a fractional calculus approach. Presented fractional-order distribution morphs into integer-order diffusion in the case of integral fractional exponents. The model demonstrates that accumulation of diffusing species can occur and the scar properties (i.e. tortuosity, fractional order, scar thickness) and boundary conditions can influence such accumulation. The observed shape of the concentration profile corresponds qualitatively with GFAP profiles reported in the literature. The main difference with respect to the previous studies is the explicit incorporation of the apparatus of fractional calculus without assumption of an ad hoc tortuosity parameter. The approach can be adapted to other studies of diffusion in biological tissues, for example of biomolecules or small drug molecules. PMID:27179458

  18. Glial fibrillary acidic protein (GFAP: modulation by growth factors and its implication in astrocyte differentiation

    Directory of Open Access Journals (Sweden)

    F.C.A. Gomes

    1999-05-01

    Full Text Available Intermediate filament (IF proteins constitute an extremely large multigene family of developmentally and tissue-regulated cytoskeleton proteins abundant in most vertebrate cell types. Astrocyte precursors of the CNS usually express vimentin as the major IF. Astrocyte maturation is followed by a switch between vimentin and glial fibrillary acidic protein (GFAP expression, with the latter being recognized as an astrocyte maturation marker. Levels of GFAP are regulated under developmental and pathological conditions. Upregulation of GFAP expression is one of the main characteristics of the astrocytic reaction commonly observed after CNS lesion. In this way, studies on GFAP regulation have been shown to be useful to understand not only brain physiology but also neurological disease. Modulators of GFAP expression include several hormones such as thyroid hormone, glucocorticoids and several growth factors such as FGF, CNTF and TGFß, among others. Studies of the GFAP gene have already identified several putative growth factor binding domains in its promoter region. Data obtained from transgenic and knockout mice have provided new insights into IF protein functions. This review highlights the most recent studies on the regulation of IF function by growth factors and hormones.

  19. Acquisition of glial cells missing 2 enhancers contributes to a diversity of ionocytes in zebrafish.

    Directory of Open Access Journals (Sweden)

    Takanori Shono

    Full Text Available Glial cells missing 2 (gcm2 encoding a GCM-motif transcription factor is expressed in the parathyroid in amniotes. In contrast, gcm2 is expressed in pharyngeal pouches (a homologous site of the parathyroid, gills, and H(+-ATPase-rich cells (HRCs, a subset of ionocytes on the skin surface of the teleost fish zebrafish. Ionocytes are specialized cells that are involved in osmotic homeostasis in aquatic vertebrates. Here, we showed that gcm2 is essential for the development of HRCs and Na(+-Cl(- co-transporter-rich cells (NCCCs, another subset of ionocytes in zebrafish. We also identified gcm2 enhancer regions that control gcm2 expression in ionocytes of zebrafish. Comparisons of the gcm2 locus with its neighboring regions revealed no conserved elements between zebrafish and tetrapods. Furthermore, We observed gcm2 expression patterns in embryos of the teleost fishes Medaka (Oryzias latipes and fugu (Fugu niphobles, the extant primitive ray-finned fishes Polypterus (Polypterus senegalus and sturgeon (a hybrid of Huso huso × Acipenser ruhenus, and the amphibian Xenopus (Xenopus laevis. Although gcm2-expressing cells were observed on the skin surface of Medaka and fugu, they were not found in Polypterus, sturgeon, or Xenopus. Our results suggest that an acquisition of enhancers for the expression of gcm2 contributes to a diversity of ionocytes in zebrafish during evolution.

  20. Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems.

    Science.gov (United States)

    Köles, László; Kató, Erzsébet; Hanuska, Adrienn; Zádori, Zoltán S; Al-Khrasani, Mahmoud; Zelles, Tibor; Rubini, Patrizia; Illes, Peter

    2016-03-01

    Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. PMID:26542977

  1. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  2. Comparative Analysis of Human, Mouse, and Pig Glial Fibrillary Acidic Protein Gene Structures.

    Science.gov (United States)

    Eun, Kiyoung; Hwang, Seon-Ung; Jeon, Hye-Min; Hyun, Sang-Hwan; Kim, Hyunggee

    2016-01-01

    Comparing the coding and regulatory sequences of genes in different species provides information on whether proteins translated from genes have conserved functions or gene expressions are regulated by analogical mechanisms. Herein, we compared the coding and regulatory sequences of glial fibrillary acidic protein (GFAP) from humans, mice, and pigs. The GFAP gene encodes a class III intermediate filament protein expressed specifically in astrocytes of the central nervous system. On comparing the mRNA, regulatory region (promoter), and protein sequences of GFAP gene in silico, we found that GFAP mRNA 3'-untranslated region (3'-UTR), promoter, and amino acid sequences showed higher similarities between humans and pigs than between humans and mice. In addition, the promoter-luciferase reporter gene assay revealed that the pig GFAP promoter functioned in human astrocytes. Notably, the 1.8-kb promoter fragment upstream from transcription initiation site showed strongest transcriptional activity compared to 5.2-kb DNA fragment or other regions of GFAP promoter. We also found that pig GFAP mRNA and promoter activity increased in pig fibroblasts by human IL-1β treatment. Taken together, these results suggest that the regulatory mechanisms and functions of pig genes might be more similar to those of humans than mice, indicating that pigs, particularly miniature pigs, are a useful model for studying human biological and pathological events. PMID:26913554

  3. Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish.

    Science.gov (United States)

    Pellegrini, Elisabeth; Diotel, Nicolas; Vaillant-Capitaine, Colette; Pérez Maria, Rita; Gueguen, Marie-Madeleine; Nasri, Ahmed; Cano Nicolau, Joel; Kah, Olivier

    2016-06-01

    Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis. Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed. PMID:26151741

  4. Role of glial cells in innate immunity and their role in CNS demyelination.

    Science.gov (United States)

    Sriram, Subramaniam

    2011-10-28

    The adaptive and innate arms of the immune system are the two pillars of host defense against environmental pathogens. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS which is considered to be autoimmune and is thought to result from breakdown in the usual checks and balances of the adaptive immune response. The major pathological outcome of the disease is "the MS plaque" a unique feature of CNS demyelination characterized by the destruction of oligodendrocytes with loss of myelin and underlying axons. The MS plaque is not seen in other inflammatory disorders of the CNS. The prevailing opinion suggests that MS is mediated by the activation of an adaptive immune response which targets neural antigens. Currently, the role of an innate immune in the development of the lesions in MS has remained unclear. We explore the potential cellular elements of the innate immune system and in particular glial cells, which are likely candidates in inducing the specific pathological picture that is evident in MS. Activated microglia and the release of molecules which are detrimental to oligodendrocyte have been suggested as mechanisms by which innate immunity causes demyelination in MS. However a microglia/macrophage centric model does not explain the specificity of lesion development in MS. We propose that activation pathways of receptors of the innate immune system present on oligodendrocytes and astrocytes rather than microglia are central to the pathogenesis of demyelination seen in MS. PMID:21907419

  5. Regulation of Glial Cell Functions by PPAR-γ Natural and Synthetic Agonists

    Directory of Open Access Journals (Sweden)

    Luisa Minghetti

    2008-04-01

    Full Text Available In the recent years, the peroxisome proliferator-activated receptor-γ (PPAR-γ, a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-γ agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Δ12,14 prostaglandin J2, and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-γ agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes, as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-γ agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation.

  6. Prospective therapies for high-grade glial tumours: A literature review

    Directory of Open Access Journals (Sweden)

    Sayed Samed Talibi

    2014-09-01

    Full Text Available After three decades of intensive research, cytoreductive surgery remains the gold standard of treatment of malignant gliomas. Survivorship at both 1-year and 5-years has not drastically changed in the UK. Concomitant chemo- and radiotherapy has enhanced the efficiency of surgery, enabling more aggressive tumour resection whilst also preserving the surrounding healthy brain parenchyma. More accurate imaging techniques have also played a role in tumour identification, key to this has been pre- and intra-operative contrast enhancement and compounds that have a high affinity in binding to glioma cells. Intra-operative imaging has heralded the ability to give the operating surgeon continuous feedback to assess the completeness of resection. Research is shifting into investigating the complex cellular and molecular glial tumour-genesis, and has led to the development of efficacious chemotherapy agents and trial novel therapies. Oncolytic virotherapy has shown promise in clinical trials and gene therapy in-vitro studies. Surgery however remains the primary therapeutic option for the management of malignant gliomas removing the mass of proliferating malignant tumour cells and decompression of the space-occupying lesion.

  7. Characterization of Olfactory Ensheathing Glial Cells Cultured on Polyurethane/Polylactide Electrospun Nonwovens

    Directory of Open Access Journals (Sweden)

    Jakub Grzesiak

    2015-01-01

    Full Text Available The aim of this research was to evaluate novel biomaterials for neural regeneration. The investigated materials were composed of polyurethane (PU and polylactide (PLDL blended at three different w/w ratios, that is, 5/5, 6/4, and 8/2 of PU/PLDL. Ultrathin fibrous scaffolds were prepared using electrospinning. The scaffolds were investigated for their applicability for nerve regeneration by culturing rat olfactory ensheathing glial cells. Cells were cultured on the materials for seven days, during which cellular morphology, phenotype, and metabolic activity were analysed. SEM analysis of the fabricated fibrous scaffolds showed fibers of a diameter mainly lower than 600 μm with unimportant volume of protrusions situated along the fibers, with nonsignificant differences between all analysed materials. Cells cultured on the materials showed differences in their morphology and metabolic activity, depending on the blend composition. The most proper morphology, with numerous p75+ and GFAP+ cells present, was observed in the sample 6/4, whereas the highest metabolic activity was measured in the sample 5/5. However, none of the investigated samples showed cytotoxicity or negatively influenced cellular morphology. Therefore, the novel electrospun fibrous materials may be considered for regenerative medicine applications, and especially when contacting with highly sensitive nervous cells.

  8. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    Directory of Open Access Journals (Sweden)

    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  9. Molecular cloning and primary structure of human glial fibrillary acidic protein

    International Nuclear Information System (INIS)

    Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in astroglia. Therefore, the authors isolated a cDNA clone encoding this protein and determined its nucleotide sequence. The predicted amino acid sequence indicates that GFAP shares structural similarities-particularly in the central rod domain and to a lesser degree in the carboxyl-terminal domain-with other IF proteins found in nonepithelial cell types. Considerable sequence divergence in the amino-terminal region of GFAP suggests that the tissue-specific functions of this IF protein might be mediated through this region of the molecule. In contrast, conservation of structural characteristics and a moderate degree of sequence conservation in the carboxyl-terminal region suggest functional similarities. Blot hybridization analysis using the GFAP cDNA as a probe failed to detect GFAP mRNA in both normal and neoplastic human tissues in which IF proteins other than GFAP are known to be expressed

  10. Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior.

    Science.gov (United States)

    Arezoomandan, Reza; Khodagholi, Fariba; Haghparast, Abbas

    2016-04-01

    Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction. PMID:26547198

  11. Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.

    Science.gov (United States)

    Takeuchi, Ryoko; Toyoshima, Yasuko; Tada, Mari; Tanaka, Hidetomo; Shimizu, Hiroshi; Shiga, Atsushi; Miura, Takeshi; Aoki, Kenju; Aikawa, Akane; Ishizawa, Shin; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD. PMID:25787090

  12. Membrane-bound catechol-O-methyl transferase in cortical neurons and glial cells is intracellularly oriented

    Directory of Open Access Journals (Sweden)

    Björn H Schott

    2010-10-01

    Full Text Available Catechol-O-methyl transferase (COMT is involved in the inactivation of dopamine in brain regions in which the dopamine transporter (DAT1 is sparsely expressed. The membrane-bound isoform of COMT (MB-COMT is the predominantly expressed form in the mammalian central nervous system (CNS. It has been a matter of debate whether in neural cells of the CNS the enzymatic domain of MB-COMT is oriented towards the cytoplasmic or the extracellular compartment. Here we used live immunocytochemistry on cultured neocortical neurons and glial cells to investigate the expression and membrane orientation of native COMT and of transfected MB-COMT fused to green fluorescent protein (GFP. After live staining, COMT immunoreactivity was reliably detected in both neurons and glial cells after permeabilization, but not on unpermeabilized cells. Similarly, autofluorescence of COMT-GFP fusion protein and antibody fluorescence showed overlap only in permeabilized neurons. Our data provide converging evidence for an intracellular membrane orientation of MB-COMT in neurons and glial cells, suggesting the presence of a DAT1-independent postsynaptic uptake mechanism for dopamine, prior to its degradation via COMT.

  13. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. PMID:21352890

  14. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen

    OpenAIRE

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

    2012-01-01

    Glial calcium (Ca2+) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca2+ waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of...

  15. Attention-deficit hyperactivity disorder (ADHD and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

    Directory of Open Access Journals (Sweden)

    Schwarz Markus J

    2010-05-01

    Full Text Available Abstract Background Children with attention-deficit/hyperactivity disorder (ADHD show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity. Method We pursued one test of the idea with measures of a neurotrophin reflecting glial integrity (S100B and the influences of 8 cytokines on the metabolism of amino-acids, and of tryptophan/kynurenine to neuroprotective or potentially toxic products that could modulate glial function. Serum samples from 21 medication-naïve children with ADHD, 21 typically-developing controls, 14 medicated children with ADHD and 7 healthy siblings were analysed in this preliminary exploration of group differences and associations. Results There were no marked group differences in levels of S100B, no major imbalance in the ratios of pro- to anti-inflammatory interleukins nor in the metabolism of kynurenine to toxic metabolites in ADHD. However, four trends are described that may be worthy of closer examination in a more extensive study. First, S100B levels tended to be lower in ADHD children that did not show oppositional/conduct problems. Second, in medicated children raised interleukin levels showed a trend to normalisation. Third, while across all children the sensitivity to allergy reflected increased levels of IL-16 and IL-10, the latter showed a significant inverse relationship to measures of S100B in the ADHD group. Fourthly, against expectations healthy controls tended to show higher levels of toxic 3-hydroxykynurenine (3 HK than those with ADHD. Conclusions Thus, there were no clear signs (S100B that the glial functions were compromised in ADHD. However, other markers of glial function require examination. Nonetheless there is preliminary evidence that a minor imbalance of the immunological system was improved on medication. Finally, if lower levels of the potentially toxic 3

  16. Neural and glial progenitor transplantation as a neuroprotective strategy for Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Haidet-Phillips, Amanda M; Maragakis, Nicholas J

    2015-12-01

    ALS is a neurodegenerative disease with a prevalence rate of up to 7.4/100,000 and the overall risk of developing ALS over a lifetime is 1:400. Most patients die from respiratory failure following a course of progressive weakness. To date, only one traditional pharmaceutical agent-riluzole, has been shown to afford a benefit on survival but numerous pharmaceutical interventions have been studied in preclinical models of ALS without subsequent translation to patient efficacy. Despite the relative selectivity of motor neuron cell death, animal and tissue culture models of familial ALS suggest that non-neuronal cells significantly contribute to neuronal dysfunction and death. Early efforts to transplant stem cells had focused on motor neuron replacement. More practically for this aggressive neurodegenerative disease, recent studies, preclinical efforts, and early clinical trials have focused on the transplantation of neural stem cells, mesenchymal stem cells, or glial progenitors. Using transgenic mouse or rat models of ALS, a number of studies have shown neuroprotection through a variety of different mechanisms that have included neurotrophic factor secretion, glutamate transporter regulation, and modulation of neuroinflammation, among others. However, given that cell replacement could involve a number of biologically relevant factors, identifying the key pathway(s) that may contribute to neuroprotection remains a challenge. Nevertheless, given the abundant data supporting the interplay between non-neuronal cell types and motor neuron disease propagation, the replacement of disease-carrying host cells by normal cells may be sufficient to confer neuroprotection. Key preclinical issues that currently are being addressed include the most appropriate methods and routes for delivery of cells to disease-relevant regions of the neuraxis, cell survival and migration, and tracking the cells following transplantation. Central to the initial development of stem cell

  17. Magnetic resonance diffusion and perfusion imaging in differentiation and grading the diffuse glial brain neoplasms

    International Nuclear Information System (INIS)

    Gliomas are the most common primary brain tumors. They are heterogenous group of tumors, which have infiltrative growth and relative resistance to radio-and chemotherapy. Gliomas are estimated from the WHO classification by means of grades from I go IV. Grade I (localized, 'special' gliomas) and grade II (diffuse gliomas) are considered low-grade, while grade III, IV are high-grade. Although histologically benign, the majority of grade II tumors will transform into malignant grades III and IV during the interval 5-10 years from the initial diagnosis. Glial tumor grading is based on a histo-pathological analysis of the most malignant tumour region, and takes into account the number of mitoses, nuclear atypia, microvascular proliferation and presence of necrosis. These grade are important, because they determine the therapeutic approach and the prognosis in patients with gliomas. Conventional MR images provide important information about contrast-enhancement, oedema, distant tumoral focuses, hemorrhage, necrosis, mass effect and etc, which are very useful in assessment of the tumor aggressiveness and hence tumor grade. Contrast-enhancement reflects the blood-brain-barrier status and could not be a reliable marker of malignancy. Modern physiological MR techniques like MR diffusion and MR perfusion imaging provide information about tumor physiology like microvascularity, angiogenesis and cellularity, all of which are also important in defining the tumor grade. Diffusion weighted imaging estimates the tumor structure-cellularity and water content. Perfusion weighted imaging shows capillary density and neovascularization. (authors) Key words: DIFFUSE GLIOMAS. GLIOMA GRADE. DIFFUSION WEIGHTED AND PERFUSION WEIGHTED MAGNETIC RESONANCE IMAGING

  18. The autophagic- lysosomal pathway determines the fate of glial cells under manganese- induced oxidative stress conditions.

    Science.gov (United States)

    Gorojod, R M; Alaimo, A; Porte Alcon, S; Pomilio, C; Saravia, F; Kotler, M L

    2015-10-01

    Manganese (Mn) overexposure is frequently associated with the development of a neurodegenerative disorder known as Manganism. The Mn-mediated generation of reactive oxygen species (ROS) promotes cellular damage, finally leading to apoptotic cell death in rat astrocytoma C6 cells. In this scenario, the autophagic pathway could play an important role in preventing cytotoxicity. In the present study, we found that Mn induced an increase in the amount and total volume of acidic vesicular organelles (AVOs), a process usually related to the activation of the autophagic pathway. Particularly, the generation of enlarged AVOs was a ROS- dependent event. In this report we demonstrated for the first time that Mn induces autophagy in glial cells. This conclusion emerged from the results obtained employing a battery of autophagy markers: a) the increase in LC3-II expression levels, b) the formation of autophagic vesicles labeled with monodansylcadaverine (MDC) or LC3 and, c) the increase in Beclin 1/ Bcl-2 and Beclin 1/ Bcl-X(L) ratio. Autophagy inhibition employing 3-MA and mAtg5(K130R) resulted in decreased cell viability indicating that this event plays a protective role in Mn- induced cell death. In addition, mitophagy was demonstrated by an increase in LC3 and TOM-20 colocalization. On the other hand, we proposed the occurrence of lysosomal membrane permeabilization (LMP) based in the fact that cathepsins B and D activities are essential for cell death. Both cathepsin B inhibitor (Ca-074 Me) or cathepsin D inhibitor (Pepstatin A) completely prevented Mn- induced cytotoxicity. In addition, low dose of Bafilomycin A1 showed a similar effect, a finding that adds evidence about the lysosomal role in Mn cytotoxicity. Finally, in vivo experiments demonstrated that Mn induces injury and alters LC3 expression levels in rat striatal astrocytes. In summary, our results demonstrated that autophagy is activated to counteract the harmful effect caused by Mn. These data is valuable to

  19. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  20. HDAC1 regulates the proliferation of radial glial cells in the developing Xenopus tectum.

    Science.gov (United States)

    Tao, Yi; Ruan, Hangze; Guo, Xia; Li, Lixin; Shen, Wanhua

    2015-01-01

    In the developing central nervous system (CNS), progenitor cells differentiate into progeny to form functional neural circuits. Radial glial cells (RGs) are a transient progenitor cell type that is present during neurogenesis. It is thought that a combination of neural trophic factors, neurotransmitters and electrical activity regulates the proliferation and differentiation of RGs. However, it is less clear how epigenetic modulation changes RG proliferation. We sought to explore the effect of histone deacetylase (HDAC) activity on the proliferation of RGs in the visual optic tectum of Xenopus laevis. We found that the number of BrdU-labeled precursor cells along the ventricular layer of the tectum decrease developmentally from stage 46 to stage 49. The co-labeling of BrdU-positive cells with brain lipid-binding protein (BLBP), a radial glia marker, showed that the majority of BrdU-labeled cells along the tectal midline are RGs. BLBP-positive cells are also developmentally decreased with the maturation of the brain. Furthermore, HDAC1 expression is developmentally down-regulated in tectal cells, especially in the ventricular layer of the tectum. Pharmacological blockade of HDACs using Trichostatin A (TSA) or Valproic acid (VPA) decreased the number of BrdU-positive, BLBP-positive and co-labeling cells. Specific knockdown of HDAC1 by a morpholino (HDAC1-MO) decreased the number of BrdU- and BLBP-labeled cells and increased the acetylation level of histone H4 at lysine 12 (H4K12). The visual deprivation-induced increase in BrdU- and BLBP-positive cells was blocked by HDAC1 knockdown at stage 49 tadpoles. These data demonstrate that HDAC1 regulates radial glia cell proliferation in the developing optical tectum of Xenopus laevis. PMID:25789466

  1. Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

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    Jacobs Mary B

    2009-08-01

    Full Text Available Abstract Background Lyme neuroborreliosis (LNB may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS, and dorsal root nerves and ganglia (DRG. Results ELISA of the cerebrospinal fluid (CSF showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Conclusion Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

  2. Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned

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    Viktoria eGudi

    2014-03-01

    Full Text Available Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS and other central nervous system (CNS lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and grey matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and grey matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination.The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.

  3. Role of glutamate receptors and glial cells in the pathophysiology of treatment-resistant depression.

    Science.gov (United States)

    Kim, Yong-Ku; Na, Kyoung-Sae

    2016-10-01

    Treatment-resistant depression (TRD) causes substantial socioeconomic burden. Although a consensus on the definition of TRD has not yet been reached, it is certain that classic monoaminergic antidepressants are ineffective for TRD. One decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, to be an alternative to classic monoaminergic antidepressants. The major mechanisms of action of ketamine rapidly induce synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway. Although excessive glutamatergic neurotransmission and consequent excitotoxicity were considered a major cause of TRD, recent evidence suggests that the extrasynaptic glutamatergic receptor signal pathway mainly contributes to the detrimental effects of TRD. Glial cells such as microglia and astrocytes, early life adversity, and glucocorticoid receptor dysfunction participate in complex cross-talk. An appropriate reuptake of glutamate at the astrocyte is crucial for preventing 'spill-over' of synaptic glutamate and binding to the extrasynaptic NMDA receptor. Excessive microglial activation and the inflammatory process cause astrocyte glutamatergic dysfunction, which in turn activates microglial function. Early life adversity and glucocorticoid receptor dysfunction result in vulnerability to stress in adulthood. A maladaptive response to stress leads to increased glutamatergic release and pro-inflammatory cytokines, which then activate microglia. However, since the role of inflammatory mediators such as pro-inflammatory cytokines is not specific for depression, more disease-specific mechanisms should be identified. Last, although much research has focused on ketamine as an alternative antidepressant for TRD, its long-lasting effectiveness and adverse events have not been rigorously demonstrated. Additionally, evidence suggests that substantial brain abnormalities develop in ketamine abusers. Thus, more investigations for ketamine and other novel

  4. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.

    Science.gov (United States)

    Almeida, Cayo; DeMaman, Aline; Kusuda, Ricardo; Cadetti, Flaviane; Ravanelli, Maria Ida; Queiroz, André L; Sousa, Thais A; Zanon, Sonia; Silveira, Leonardo R; Lucas, Guilherme

    2015-03-01

    Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain. PMID:25687543

  5. Lower glial metabolite levels in brains of young children with prenatal nicotine exposure.

    Science.gov (United States)

    Chang, Linda; Cloak, Christine C; Jiang, Caroline S; Hoo, Aaron; Hernandez, Antonette B; Ernst, Thomas M

    2012-03-01

    Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/(1)H MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions. Children with PNE had similar performance to controls on neuropsychological testing. However, compared to controls, the PNE group had lower MI (repeated measures ANOVA-p = 0.03) and tCr levels (repeated measures ANOVA-p = 0.003), especially in the basal ganglia of the girls (-19.3%, p = 0.01). In contrast, GLX was elevated in the anterior cingulate cortex of the PNE children (+9.4%, p = 0.03), and those with the highest GLX levels had the poorest performance on vocabulary (r = -0.67; p metabolite concentrations. These findings suggest that PNE may lead to subclinical abnormalities in glial development, especially in the basal ganglia, and regionally specific changes in other neurometabolites. These alterations were not influenced by the amount of nicotine exposure prenatally. However, the effects of PNE on energy metabolism may be sex specific, with greater alterations in girls. PMID:21912896

  6. Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats.

    Science.gov (United States)

    Perez, Matheus; Benitez, Suzana U; Cartarozzi, Luciana P; Del Bel, Elaine; Guimarães, Francisco S; Oliveira, Alexandre L R

    2013-11-01

    In neonatal rats, the transection of a peripheral nerve leads to an intense retrograde degeneration of both motor and sensory neurons. Most of the axotomy-induced neuronal loss is a result of apoptotic processes. The clinical use of neurotrophic factors is difficult due to side effects and elevated costs, but other molecules might be effective and more easily obtained. Among them, some are derived from Cannabis sativa. Cannabidiol (CBD) is the major non-psychotropic component found on the surface of such plant leaves. The present study aimed to investigate the neuroprotective potential of CBD. Thus, 2-day-old Wistar rats were divided into the following experimental groups: sciatic nerve axotomy + CBD treatment (CBD group), axotomy + vehicle treatment (phosphate buffer group) and a control group (no-treatment group). The results were analysed by Nissl staining, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling at 5 days post-lesion. Neuronal counting revealed both motor and sensory neuron rescue following treatment with CBD (15 and 30 mg/kg). Immunohistochemical analysis (obtained by synaptophysin staining) revealed 30% greater synaptic preservation within the spinal cord in the CBD-treated group. CBD administration decreased the astroglial and microglial reaction by 30 and 27%, respectively, as seen by glial fibrillary acidic protein and ionised calcium binding adaptor molecule 1 immunolabeling quantification. In line with such results, the terminal deoxynucleotidyl transferase dUTP nick end labeling reaction revealed a reduction of apoptotic cells, mostly located in the spinal cord intermediate zone, where interneurons promote sensory-motor integration. The present results show that CBD possesses neuroprotective characteristics that may, in turn, be promising for future clinical use. PMID:23981015

  7. Molecular signatures of cell cycle transcripts in the pathogenesis of Glial tumors

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    Bhattacharya Rabindra

    2004-01-01

    Full Text Available Abstract Background Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. These tumors form an interesting group of cancer to understand the molecular mechanism of pathogenesis. Histological grading of Astrocytoma based on WHO classification does not provide complete information on the proliferation potential and biological behavior of the tumors. It is known that cancer results from the disruption of the orderly regulated cycle of replication and division. In the present study, we made an attempt to identify the cell cycle signatures and their involvement in the clinical aggressiveness of gliomas. Methods The variation in expression of various cell cycle genes was studied in different stages of glial tumor progression (low and high grades, and the results were compared with their corresponding expression levels in the normal brain tissue. Macroarray analysis was used for the purpose. Results Macroarray analysis of 114 cell cycle genes in different grades of glioma indicated differential expression pattern in 34% of the gene transcripts, when compared to the normal tissue. Majority of the transcripts belong to the intracellular kinase networks, cell cycle regulating kinases, transcription factors and transcription activators. Conclusion Based on the observation in the expression pattern in low grade and high grade gliomas, it can be suggested that the upregulation of cell cycle activators are seen as an early event in glioma; however, in malignancy it is not the cell cycle activators alone, which are involved in tumorigenesis. Understanding the molecular details of cell cycle regulation and checkpoint abnormalities in cancer could offer an insight into potential therapeutic strategies.

  8. Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

    Directory of Open Access Journals (Sweden)

    Marta Amigó-Correig

    Full Text Available This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism.Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed.Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus.Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.

  9. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten Joan;

    2013-01-01

    Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen sa...

  10. Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

    Directory of Open Access Journals (Sweden)

    Akio Takeuchi

    Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

  11. Rat ciliary neurothrophic factor (CNTF): gene structure and regulation of mRNA levels in glial cell cultures.

    OpenAIRE

    Carroll, Patrick; Sendtner, Michael; Meyer, Michael; Thoenen, Hans

    2009-01-01

    The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyteenriched c...

  12. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    OpenAIRE

    Lufan Li; Min Wang; Mei Wang; Xiaoxi Wu; Lei Geng; Yuanyuan Xue; Xiang Wei; Yuanyuan Jia; Xin Wu

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in v...

  13. Lipid-mediated glial cell line-derived neurotrophic factor gene transfer to cultured porcine ventral mesencephalic tissue

    DEFF Research Database (Denmark)

    Bauer, Matthias; Meyer, Morten; Brevig, Thomas;

    2002-01-01

    -mediated transfer of the gene for human glial cell line-derived neurotrophic factor (GDNF) to embryonic (E27/28) porcine VM tissue kept as organotypic explant cultures. Treatment of the developing VM with two mitogens, basic fibroblast growth factor and epidermal growth factor, prior to transfection significantly...... increased transfection yields. Expression of human GDNF via an episomal vector could be detected by in situ hybridization and by the measuring of GDNF protein secreted into the culture medium. When compared to mock-transfected controls, VM tissue expressing recombinant GDNF contained significantly higher...

  14. Basic fibroblast growth factor contributes to a shift in the angioregulatory activity of retinal glial (Muller cells.

    Directory of Open Access Journals (Sweden)

    Yousef Yafai

    Full Text Available Basic fibroblast growth factor (bFGF is a pleiotropic cytokine with pro-angiogenic and neurotrophic effects. The angioregulatory role of this molecule may become especially significant in retinal neovascularization, which is a hallmark of a number of ischemic eye diseases. This study was undertaken to reveal expression characteristics of bFGF, produced by retinal glial (Müller cells, and to determine conditions under which glial bFGF may stimulate the proliferation of retinal microvascular endothelial cells. Immunofluorescence labeling detected bFGF in Müller cells of the rat retina and in acutely isolated Müller cells with bFGF levels, which increased after ischemia-reperfusion in postischemic retinas. In patients with proliferative diabetic retinopathy or myopia, the immunoreactivity of bFGF co-localized to glial fibrillary acidic protein (GFAP-positive cells in surgically excised retinal tissues. RT-PCR and ELISA analyses indicated that cultured Müller cells produce bFGF, which is elevated under hypoxia or oxidative stress, as well as under stimulation with various growth factors and cytokines, including pro-inflammatory factors. When retinal endothelial cells were cultured in the presence of media from hypoxia (0.2%-conditioned Müller cells, a distinct picture of endothelial cell proliferation emerged. Media from 24-h cultured Müller cells inhibited proliferation, whereas 72-h conditioned media elicited a stimulatory effect. BFGF-neutralizing antibodies suppressed the enhanced endothelial cell proliferation to a similar extent as anti-VEGF antibodies. Furthermore, phosphorylation of extracellular signal-regulated kinases (ERK-1/-2 in retinal endothelial cells was increased when the cells were cultured in 72-h conditioned media, while neutralizing bFGF attenuated the activation of this signaling pathway. These data provide evidence that retinal (glial Müller cells are major sources of bFGF in the ischemic retina. Müller cells under

  15. Efficient Differentiation of Embryonic Stem Cells into Neurons in Glial Cell-conditioned Medium under Attaching Conditions

    Institute of Scientific and Technical Information of China (English)

    Hai-Bin TIAN; Zeng-Liang BAI; Hong WANG; Jian-Quan CHEN; Guo-Xiang CHENG

    2005-01-01

    Embryonic stem (ES) cells can differentiate into neurons in vitro, which provides hope for the treatment of some neurodegenerative diseases through cell transplantation. However, it remains a challenge to efficiently induce ES cells to differentiate into neurons. Here, we show that murine ES cells can efficiently differentiate into neurons when cultured in glial cell- conditioned medium (GCM) under attaching conditions without the formation of embryoid bodies. In comparison with murine embryonic fibroblast-conditioned medium, we found that GCM has a positive effect on limiting the generation of non-neuronal cells, such as astrocytes. In addition, compared with suspension conditions, attaching conditions delay the differentiation process of ES cells.

  16. Neuroimaging findings of the post-treatment effects of radiation and chemotherapy of malignant primary glial neoplasms.

    Science.gov (United States)

    Mamlouk, M D; Handwerker, J; Ospina, J; Hasso, A N

    2013-08-01

    Post-treatment radiation and chemotherapy of malignant primary glial neoplasms present a wide spectrum of tumor appearances and treatment-related entities. Radiologic findings of these post-treatment effects overlap, making it difficult to distinguish treatment response and failure. The purposes of this article are to illustrate and contrast the imaging appearances of recurrent tumor from necrosis and to discuss other radiologic effects of cancer treatments. It is critical for radiologists to recognize these treatment-related effects to help direct clinical management. PMID:24007728

  17. Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor for repair of spinal cord contusion injury

    Institute of Scientific and Technical Information of China (English)

    Alireza Abdanipour; Taki Tiraihi; Taher Taheri

    2014-01-01

    To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord con-tusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neuro-trophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These ifndings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.

  18. Indirect effects of TiO2 nanoparticle on neuron-glial cell interactions.

    Science.gov (United States)

    Hsiao, I-Lun; Chang, Chia-Cheng; Wu, Chung-Yi; Hsieh, Yi-Kong; Chuang, Chun-Yu; Wang, Chu-Fang; Huang, Yuh-Jeen

    2016-07-25

    Although, titanium dioxide nanoparticles (TiO2NPs) are nanomaterials commonly used in consumer products, little is known about their hazardous effects, especially on central nervous systems. To examine this issue, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were exposed to 6 nm of 100% anatase TiO2NPs. A lipopolysaccharide (LPS) was pre-treated to activate glial cells before NP treatment for mimicking NP exposure under brain injury. We found that ALT and BV-2 cells took up more NPs than N2a cells and caused lower cell viability. TiO2NPs induced IL-1β in the three cell lines and IL-6 in N2a. LPS-activated BV-2 took up more TiO2NPs than normal BV-2 and released more intra/extracellular reactive oxygen species (ROS), IL-1β, IL-6 and MCP-1 than did activated BV-2. Involvement of clathrin- and caveolae-dependent endocytosis in ALT and clathrin-dependent endocytosis and phagocytosis in BV-2 both had a slow NP translocation rate to lysosome, which may cause slow ROS production (after 24 h). Although TiO2NPs did not directly cause N2a viability loss, by indirect NP exposure to the bottom chamber of LPS-activated BV-2 in the Transwell system, they caused late apoptosis and loss of cell viability in the upper N2a chamber due to H2O2 and/or TNF-α release from BV-2. However, none of the adverse effects in N2a or BV-2 cells was observed when TiO2NPs were exposed to ALT-N2a or ALT-BV-2 co-culture. These results demonstrate that neuron damage can result from TiO2NP-mediated ROS and/or cytokines release from microglia, but not from astrocytes. PMID:27216632

  19. Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method

    Energy Technology Data Exchange (ETDEWEB)

    Cebeci, H, E-mail: hcebeci16@gmail.com [Department of Radiology, Uludag University Medical School, Bursa (Turkey); Aydin, O [Department of Radiology, Uludag University Medical School, Bursa (Turkey); Ozturk-Isik, E; Gumus, C [Department of Biomedical Engineering, Yeditepe University, Istanbul (Turkey); Inecikli, F [Department of Radiology, Kanuni Sultan Suleyman Educational and Research Hospital, Istanbul (Turkey); Bekar, A; Kocaeli, H [Department of Neurosurgery, Uludag University Medical School, Bursa (Turkey); Hakyemez, B [Department of Radiology, Uludag University Medical School, Bursa (Turkey)

    2014-10-15

    Highlights: • We compared the perfusion parameters obtained with both DSC and ASL perfusion imaging methods. • In ASL perfusion imaging, we also created quantitative CBF maps. • All patients included in the study had histopathological diagnose. • All MR examinations are done with 3T MR imaging system. - Abstract: Purpose: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. Methods: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann–Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using

  20. Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method

    International Nuclear Information System (INIS)

    Highlights: • We compared the perfusion parameters obtained with both DSC and ASL perfusion imaging methods. • In ASL perfusion imaging, we also created quantitative CBF maps. • All patients included in the study had histopathological diagnose. • All MR examinations are done with 3T MR imaging system. - Abstract: Purpose: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. Methods: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann–Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using

  1. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  2. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Institute of Scientific and Technical Information of China (English)

    Feng Xue; Er-jun Wu; Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Na Han

    2015-01-01

    We examined the restorative effect of modiifed biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantationin vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial ifbrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve ifbers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our ifndings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvi-ronment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  3. Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression.

    Science.gov (United States)

    Li, Lu-Fan; Yang, Jie; Ma, Shi-Ping; Qu, Rong

    2013-07-01

    Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. PMID:23632393

  4. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine.

    Science.gov (United States)

    Zadina, James E; Nilges, Mark R; Morgenweck, Jenny; Zhang, Xing; Hackler, Laszlo; Fasold, Melita B

    2016-06-01

    Opioids acting at the mu opioid receptor (MOR) are the most effective analgesics, however adverse side effects severely limit their use. Of particular importance, abuse liability results in major medical, societal, and economic problems, respiratory depression is the cause of fatal overdoses, and tolerance complicates treatment and increases the risk of side effects. Motor and cognitive impairment are especially problematic for older adults. Despite the host of negative side effects, opioids such as morphine are commonly used for acute and chronic pain conditions. Separation of analgesia from unwanted effects has long been an unmet goal of opioid research. Novel MOR agonist structures may prove critical for greater success. Here we tested metabolically stable analogs of the endomorphins, endogenous opioids highly selective for the MOR. Compared to morphine, the analogs showed dramatically improved analgesia-to-side-effect ratios. At doses providing equal or greater antinociception than morphine in the rat, the analogs showed reduced a) respiratory depression, b) impairment of motor coordination, c) tolerance and hyperalgesia, d) glial p38/CGRP/P2X7 receptor signaling, and e) reward/abuse potential in both conditioned place preference and self-administration tests. Differential effects on glial activation indicate a mechanism for the relative lack of side effects by the analogs compared to morphine. The results suggest that endomorphin analogs described here could provide gold standard pain relief mediated by selective MOR activation, but with remarkably safer side effect profiles compared to opioids like morphine. PMID:26748051

  5. A preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro.

    Directory of Open Access Journals (Sweden)

    Michael D Coleman

    Full Text Available Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

  6. Effects of photoreceptor metabolism on interstitial and glial cell pH in bee retina: evidence of a role for NH4+.

    Science.gov (United States)

    Coles, J A; Marcaggi, P; Véga, C; Cotillon, N

    1996-09-01

    1. Measurements were made with pH microelectrodes in superfused slices of the retina of the honey-bee drone. In the dark, the mean +/- S.E.M. pH values in the three compartments of the tissue were: neurones (photoreceptors), 6.99 +/- 0.04; glial cells (outer pigment cells), 7.31 +/- 0.03; extracellular space, 6.60 +/- 0.03. 2. Stimulation of the photoreceptors with light caused transient pH changes: a decrease in the photoreceptors (pHn) and in the glial cells (pHg), and an increase in the interstitial clefts (pHo). 3. The effects of inhibition and activation of aerobic metabolism showed that part, perhaps all, of the light-induced delta pHo resulted from the increased aerobic metabolism in the photoreceptors. 4. Addition of 2 mM NH4+ to the superfusate produced changes in pHo and pHg of the same sign as and similar amplitude to those caused by light stimulation. Manipulation of transmembrane pH gradients had similar effects on changes in pHo induced by light or by exogenous NH4+. 5. Measurements with NH(4+)-sensitive microelectrodes showed that stimulation of aerobic metabolism in the photoreceptors increased [NH4+]o and also that exogenous NH4+/NH3 was taken up by cells, presumably the glial cells. 6. We conclude that within seconds of an increase in the aerobic metabolism in the photoreceptors, they release an increased amount of NH4+/NH3 which affects pHo and enters glial cells. Other evidence suggests that in drone retina the glial cells supply the neurones with amino acids as substrates of energy metabolism; the present results suggest that fixed nitrogen is returned to the glial cells as NH4+/NH3. PMID:8887745

  7. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

    Directory of Open Access Journals (Sweden)

    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  8. Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease.

    Science.gov (United States)

    Bortolanza, Mariza; Cavalcanti-Kiwiatkoski, Roberta; Padovan-Neto, Fernando E; da-Silva, Célia Aparecida; Mitkovski, Miso; Raisman-Vozari, Rita; Del-Bel, Elaine

    2015-01-01

    l-3, 4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson's disease but can induce debilitating abnormal involuntary movements (dyskinesia). Here we show that the development of L-DOPA-induced dyskinesia in the rat is accompanied by upregulation of an inflammatory cascade involving nitric oxide. Male Wistar rats sustained unilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. After three weeks animals started to receive daily treatment with L-DOPA (30 mg/kg plus benserazide 7.5 mg/kg, for 21 days), combined with an inhibitor of neuronal NOS (7-nitroindazole, 7-NI, 30 mg/kg/day) or vehicle (saline-PEG 50%). All animals treated with L-DOPA and vehicle developed abnormal involuntary movements, and this effect was prevented by 7-NI. L-DOPA-treated dyskinetic animals exhibited an increased striatal and pallidal expression of glial fibrillary acidic protein (GFAP) in reactive astrocytes, an increased number of CD11b-positive microglial cells with activated morphology, and the rise of cells positive for inducible nitric oxide-synthase immunoreactivity (iNOS). All these indexes of glial activation were prevented by 7-NI co-administration. These findings provide evidence that the development of L-DOPA-induced dyskinesia in the rat is associated with activation of glial cells that promote inflammatory responses. The dramatic effect of 7-NI in preventing this glial response points to an involvement of nitric oxide. Moreover, the results suggest that the NOS inhibitor prevents dyskinesia at least in part via inhibition of glial cell activation and iNOS expression. Our observations indicate nitric oxide synthase inhibitors as a therapeutic strategy for preventing neuroinflammatory and glial components of dyskinesia pathogenesis in Parkinson's disease. PMID:25447229

  9. Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

    OpenAIRE

    Haj-Yasein, Nadia Nabil; Vindedal, Gry Fluge; Eilert-Olsen, Martine; Gundersen, Georg Andreas; Skare, Øivind; Laake, Petter; Klungland, Arne; Thorén, Anna Elisabeth; Burkhardt, John Michael; Ottersen, Ole Petter; Nagelhus, Erlend Arnulf

    2011-01-01

    Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood–brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence o...

  10. 缬草对慢性应激导致的抑郁大鼠血清皮质酮和海马caspase-3阳性细胞数量的影响%Effects of Valerian on serum cortisol level and caspase-3 positive cells of hippocampus in depressive rats induced by chronic mild stress

    Institute of Scientific and Technical Information of China (English)

    秦亚静; 林玉坤; 周春春; 李燕; 钟志强; 曾园山

    2009-01-01

    目的 探讨缬草对慢性应激导致的抑郁大鼠体重、行为、血清皮质醇和海马Caspase-3阳性细胞数量的影响.方法 50只大鼠被分为正常对照组、未用药模型组、阴性对照模型组、阳性对照模型组和缬草治疗组,每组各10只.除正常对照组外,给予其余4组大鼠为期4周的慢性应激,以建立抑郁症模型.在整个实验期间,每周检测所有大鼠体重、自来水摄取量、1%糖水摄取量.除未用药模型组正常饲养外,其余4组大鼠在模型建立后分别灌服羧甲基纤维素钠、氟西汀以及缬草,灌药周期均为3周.灌药结束后,每组随机选取5只大鼠,采用放射免疫法检测其血清皮质酮水平;每组另5只大鼠用于caspase-3阳性细胞的计数.结果 经过4周慢性应激后,与正常对照组大鼠相比,抑郁模型组大鼠的体重以及1%糖水摄取量明显降低.灌服缬草3周后,能使抑郁模型组大鼠的体重、1%糖水摄取量增加并恢复到正常对照组水平.缬草治疗组血清皮质酮水平明显降低,并恢复至正常对照组大鼠水平,同时使抑郁大鼠海马caspase-3阳性细胞总数减少到正常对照组大鼠水平.结论 缬草能使抑郁大鼠恢复体重及正常行为,能降低抑郁大鼠血清皮质酮水平,并具有减少大脑海马caspase-3阳性细胞的作用.

  11. Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

    Directory of Open Access Journals (Sweden)

    Sonntag William E

    2011-10-01

    Full Text Available Abstract Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months and aged (26-28 months F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG. Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6 and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a

  12. Stressor-dependent Alterations in Glycoprotein 130: Implications for Glial Cell Reactivity, Cytokine Signaling and Ganglion Cell Health in Glaucoma

    Science.gov (United States)

    Echevarria, FD; Walker, CC; Abella, SK; Won, M; Sappington, RM

    2013-01-01

    Objective: The interleukin-6 (IL-6) family of cytokines is associated with retinal ganglion cell (RGC) survival and glial reactivity in glaucoma. The purpose of this study was to evaluate glaucoma-related changes in glycoprotein-130 (gp130), the common signal transducer of the IL-6 family of cytokines, as they relate to RGC health, glial reactivity and expression of IL-6 cytokine family members. Methods: For all experiments, we examined healthy retina (young C57), aged retina (aged C57), retina predisposed to glaucoma (young DBA/2) and retina with IOP-induced glaucoma (aged DBA/2). We determined retinal gene expression of gp130 and IL-6 family members, using quantitative PCR, and protein expression of gp130, using multiplex ELISA. For protein localization and cell-specific expression, we performed co-immunolabeling for gp130 and cell type-specific markers. We used quantitative microscopy to measure layer-specific expression of gp130 and its relationships to astrocyte and Müller glia reactivity and RGC axonal transport, as determined by uptake and transport of cholera toxin β-subunit (CTB). Results: Gene expression of gp130 was elevated with all glaucoma-related stressors, but only normal aging increased protein levels. In healthy retina, gp130 localized primarily to the inner retina, where it was expressed by astrocytes, Müller cells and RGCs. Layer-specific analysis of gp130 expression revealed increased expression in aging retina and decreased expression in glaucomatous retina that was eccentricity-dependent. These glaucoma-related changes in gp130 expression correlated with the level of GFAP and glutamine synthetase expression, as well as axonal transport in RGCs. The relationships between gp130, glial reactivity and RGC health could impact signaling by many IL-6 family cytokines, which exhibited overall increased expression in a stressor-dependent manner. Conclusions: Glaucoma-related stressors, including normal aging, glaucoma predisposition and IOP

  13. Mechanisms underlying the protective effects of myricetin and quercetin following oxygen/glucose deprivation-induced cell swelling and the reduction in glutamate uptake in glial cells

    Science.gov (United States)

    C6 glial cells were exposed to oxygen-glucose deprivation (OGD) in cell culture for 5 hr and cell swelling was determined 90 min after the end of OGD. The OGD-induced increase in swelling was significantly blocked by the two flavonoids studied, quercetin and myricetin. The OGD-induced increase in ...

  14. Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

    Science.gov (United States)

    Stiene-Martin, Anne; Gurwell, Julie A.; Hauser, Kurt F.

    2016-01-01

    SUMMARY To determine whether exogenous opiate drugs with abuse liability directly modify neural growth, the present study investigated the effects of morphine on astrocyte proliferation and differentiation in primary cultures of murine glial cells. The results indicate that morphine decreases glial cell production in a dose-dependent, naloxone reversible manner. Most notably, gliogenesis virtually ceased in the presence of 10−6 M morphine during the first week in culture, whereas 10−8 M or 10−10 M morphine caused an intermediate suppression of growth compared to control or 10−6 M morphine treated cultures. Moreover, morphine-treatment inhibited [3H]thymidine incorporation by glial fibrillary acidic protein (GFAP) immunoreactive, flat (type 1) astrocytes, suggesting that the decrease in glial cell production was due in part to an inhibition of astrocyte proliferation. Morphine also caused significant increases in both cytoplasmic area and process elaboration in flat (type 1) astrocytes indicating greater morphologic differentiation. In the above experiments, morphine-dependent alterations in astrocyte growth were antagonized by naloxone, indicating that morphine action was mediated by specific opioid receptors. These observations suggest that opiate drugs can directly modify neural growth by influencing two critical developmental events in astrocytes, i.e., inhibiting proliferation and inducing morphologic differentiation. PMID:1914143

  15. Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells

    International Nuclear Information System (INIS)

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCVL, in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle in glial cells by stimulating JCV gene expression. The results suggest a mechanism for the relatively high incidence of PML in AIDS patients than in other immunosuppressive disorders. Furthermore, the findings indicate that the HIV-1 regulatory protein tat may stimulate other viral and perhaps cellular promoters, in addition to its own

  16. Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation

    Science.gov (United States)

    Cheng, Wei; Chen, Yuan-Li; Wu, Liang; Miao, Bei; Yin, Qin; Wang, Jin-Feng; Fu, Zhi-Jian

    2016-01-01

    The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain. PMID:27508024

  17. The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition

    Science.gov (United States)

    Fernandes de Lima, Vera Maura; Pereira, Alfredo

    2016-01-01

    Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions. PMID:26949548

  18. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Directory of Open Access Journals (Sweden)

    Lufan Li

    2015-09-01

    Full Text Available Spermatonial stem cells (SSCs are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF, secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0 and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998.

  19. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Science.gov (United States)

    Li, Lufan; Wang, Min; Wang, Mei; Wu, Xiaoxi; Geng, Lei; Xue, Yuanyuan; Wei, Xiang; Jia, Yuanyuan; Wu, Xin

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0) and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998). PMID:26484267

  20. The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition

    Directory of Open Access Journals (Sweden)

    Vera Maura Fernandes de Lima

    2016-01-01

    Full Text Available Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions.

  1. Sequence analysis and functional study of the Han Nationality glial cell line-derived neurotrophic factor transcript

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; HUANG Ai-jun; LU Chang-lin; WU Xiang-fu; HE Cheng

    2001-01-01

    To study the sequence and function of the glial cell line-derived neurotrophic factor (GDNF) transcript in subjects of Han nationality. Methods: The Han nationality GDNF transcript was amplified by RT-PCR and expressed by baculovirus expression system. Biological activity of the expressed product was measured by the primary culture of midbrain dopaminergic neurons. Results: There only existed the shorter GDNF transcript of 555 bp in the Han nationality. The secretory expression product of the shorter transcript in insect cells promoted the survival and differentiation of dopaminergic neurons. Conclusion: It is found that there is a 78 bp deletion in the Han nationality GDNF transcript compared with the reported 633 bp GDNF transcript. The 78 bp deletion does not affect the secretory expression and biological activity of GDNF mature protein.

  2. Therapeutic effects of NogoA vaccine and olfactory ensheathing glial cell implantation on acute spinal cord injury

    Directory of Open Access Journals (Sweden)

    Zhang Z

    2013-10-01

    Full Text Available Zhicheng Zhang, Fang Li, Tiansheng Sun, Dajiang Ren, Xiumei Liu PLA Institute of Orthopedics, Beijing Army General Hospital, Beijing, People's Republic of China Background: Many previous studies have focused on the effects of IN-1, a monoclonal antibody that neutralizes Nogo (a neurite growth inhibitory protein, on neurologic regeneration in spinal cord injury (SCI. However, safety problems and the short half-life of the exogenous antibody are still problematic. In the present study, the NogoA polypeptide was used as an antigen to make a therapeutic NogoA vaccine. Rats were immunized with this vaccine and were able to secrete the polyclonal antibody before SCI. The antibody can block NogoA within the injured spinal cord when the antibody gains access to the spinal cord due to a compromised blood–spinal cord barrier. Olfactory ensheathing glial cell transplantation has been used in a spinal cord contusion model to promote the recovery of SCI. The present study was designed to verify the efficacy and safety of NogoA polypeptide vaccine, the effects of immunotherapy with this vaccine, and the synergistic effects of the vaccine and olfactory ensheathing glial cells in repair of SCI. Methods: A 13-polypeptide fragment of NogoA was synthesized. This fragment was then coupled with keyhole limpet hemocyanin to improve the immunogenicity of the polypeptide vaccine. Immunization via injection into the abdominal cavity was performed in rats before SCI. The serum antibody level and ability of the vaccine to bind with Nogo were detected by enzyme-linked immunosorbent assay. The safety of the vaccine was evaluated according to the incidence and severity of experimental autoimmune encephalomyelitis. Olfactory ensheathing glia cells were obtained, purified, and subsequently implanted into a Wistar rat model of thoracic spinal cord contusion injury. The rats were divided into four groups, ie, an SCI model group, an olfactory ensheathing glia group, a vaccine

  3. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  4. Time-lapse imaging of the dynamics of CNS glial-axonal interactions in vitro and ex vivo.

    Directory of Open Access Journals (Sweden)

    Kalliopi Ioannidou

    Full Text Available BACKGROUND: Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination. METHODOLOGY/PRINCIPAL FINDINGS: We took two approaches to follow myelination over time: i time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii ex vivo imaging of the spinal cord of shiverer (Mbp mutant mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin. CONCLUSION: These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data.

  5. The glial cell modulator ibudilast attenuates neuroinflammation and enhances retinal ganglion cell viability in glaucoma through protein kinase A signaling.

    Science.gov (United States)

    Cueva Vargas, Jorge L; Belforte, Nicolas; Di Polo, Adriana

    2016-09-01

    Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness worldwide. Vision deficits in glaucoma result from the selective loss of retinal ganglion cells (RGC). Glial cell-mediated neuroinflammation has been proposed to contribute to disease pathophysiology, but whether this response is harmful or beneficial for RGC survival is not well understood. To test this, we characterized the role of ibudilast, a clinically approved cAMP phosphodiesterase (PDE) inhibitor with preferential affinity for PDE type 4 (PDE4). Here, we demonstrate that intraocular administration of ibudilast dampened macroglia and microglia reactivity in the retina and optic nerve hence decreasing production of proinflammatory cytokines in a rat model of ocular hypertension. Importantly, ibudilast promoted robust RGC soma survival, prevented axonal degeneration, and improved anterograde axonal transport in glaucomatous eyes without altering intraocular pressure. Intriguingly, ocular hypertension triggered upregulation of PDE4 subtype A in Müller glia, and ibudilast stimulated cAMP accumulation in these cells. Co-administration of ibudilast with Rp-cAMPS, a cell-permeable and non-hydrolysable cAMP analog that inhibits protein kinase A (PKA), completely blocked ibudilast-induced neuroprotection. Collectively, these data demonstrate that ibudilast, a safe and well-tolerated glial cell modulator, attenuates gliosis, decreases levels of proinflammatory mediators, and enhances neuronal viability in glaucoma through activation of the cAMP/PKA pathway. This study provides insight into PDE4 signaling as a potential target to counter the harmful effects associated with chronic gliosis and neuroinflammation in glaucoma. PMID:27163643

  6. Global cellular responses to β-methyl-amino-L-alanine (BMAA) by olfactory ensheathing glial cells (OEC).

    Science.gov (United States)

    Chiu, Alexander S; Braidy, Nady; Marçal, Helder; Welch, Jeffrey H; Gehringer, Michelle M; Guillemin, Gilles J; Neilan, Brett A

    2015-06-01

    This study utilised a proteomics approach to identify any differential protein expression in a glial cell line, rat olfactory ensheathing cells (OECs), treated with the cyanotoxin β-methylamino-l-alanine (BMAA). Five proteins of interest were identified, namely Rho GDP-dissociation inhibitor 1 (RhoGDP1), Nck-associated protein 1 (NCKAP1), voltage-dependent anion-selective channel protein 1 (VDAC1), 3-hydroxyacyl-CoA dehydrogenase type-2 (3hCoAdh2), and ubiquilin-4 (UBQLN4). Four of these candidates, nuclear receptor subfamily 4 group A member 1 (Nur77), cyclophilin A (CyPA), RhoGDP1 and VDAC1, have been reported to be involved in cell growth. A microarray identified UBQLN4, palladin and CyPA, which have been implicated to have roles in excitotoxicity. Moreover, the NCKAP1, UBQLN4, CyPA and 3hCoAdh2 genes have been associated with abnormal protein aggregation. Differential expression of genes involved in mitochondrial activity, Nur77, 3hCoAdh2, VDAC1 and UBQLN4, were also identified. Confirmatory reverse transcription quantitative PCR (RT-qPCR) analysis of transcripts generated from the genes of interest corroborated the differential expression trends identified in the global protein analysis. BMAA induced cell cycle arrest in the G2/M phase of OEC and apoptosis after 48 h at concentrations of 250 μM and 500 μM. Collectively, this work advances our understanding of the mechanism of BMAA-mediated glial-toxicity in vitro. PMID:25797319

  7. Glial A30P alpha-synuclein pathology segregates neurogenesis from anxiety-related behavior in conditional transgenic mice.

    Science.gov (United States)

    Marxreiter, Franz; Ettle, Benjamin; May, Verena E L; Esmer, Hakan; Patrick, Christina; Kragh, Christine Lund; Klucken, Jochen; Winner, Beate; Riess, Olaf; Winkler, Jürgen; Masliah, Eliezer; Nuber, Silke

    2013-11-01

    In Parkinson's disease (PD) patients, alpha-synuclein (α-syn) pathology advances in form of Lewy bodies and Lewy neurites throughout the brain. Clinically, PD is defined by motor symptoms that are predominantly attributed to the dopaminergic cell loss in the substantia nigra. However, motor deficits are frequently preceded by smell deficiency or neuropsychological symptoms, including increased anxiety and cognitive dysfunction. Accumulating evidence indicates that aggregation of α-syn impairs synaptic function and neurogenic capacity that may be associated with deficits in memory, learning and mood. Whether and how α-syn accumulation contributes to neuropathological events defining these earliest signs of PD is presently poorly understood. We used a tetracycline-suppressive (tet-off) transgenic mouse model that restricts overexpression of human A30P α-syn to neurons owing to usage of the neuron-specific CaMKIIα promoter. Abnormal accumulation of A30P correlated with a decreased survival of newly generated neurons in the hippocampus and olfactory bulb. Furthermore, when A30P α-syn expression was suppressed, we observed reduction of the human protein in neuronal soma. However, residual dox resistant A30P α-syn was detected in glial cells within the hippocampal neurogenic niche, concomitant with the failure to fully restore hippocampal neurogenesis. This finding is indicative to a potential spread of pathology from neuron to glia. In addition, mice expressing A30P α-syn show increased anxiety-related behavior that was reversed after dox treatment. This implies that glial A30P α-synucleinopathy within the dentate gyrus is part of a process leading to impaired hippocampal neuroplasticity, which is, however, not a sole critical event for circuits implicated in anxiety-related behavior. PMID:23867236

  8. Role of IFN-gamma and LPS on Neuron/Glial Co-Cultures Infected by Neospora caninum

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    Erica Etelvina Viana De Jesus

    2014-10-01

    Full Text Available Neospora caninum causes cattle abortion and neurological symptoms in dogs. Although infection is usually asymptomatic, classical neurological symptoms of neosporosis may be associated with encephalitis. This parasite can grow in brain endothelial cells without markedly damages, but it can modulate the cellular environment to promote its survival in the brain. In previous studies, we described that IFN-γ decreased the parasite proliferation and down regulated nitric oxide production in astrocyte/microglia cultures. However, it remains unclear how glial cells respond to N. caninum in the presence of neurons. Therefore, we evaluated the effect of 300 IU/mL IFN-γ or 1.0 μg/mL of LPS on infected rat neuron/glial co-cultures. After 72 hours of infection, LPS did not affect the mitochondrial dehydrogenase activity. However, IFN-γ decreased this parameter by 15.5 and 12.0% in uninfected and infected cells, respectively. The number of tachyzoites decreased 54.1 and 44.3% in cells stimulated with IFN-γ and LPS, respectively. Infection or LPS treatment did not change NO production. On the other hand, IFN-γ induced increased nitrite release in 55.7%, but the infection reverted this induction. IL-10 levels increased only in infected cultures (treated or not, meanwhile PGE2 release was improved in IFN-γ/infected or LPS/infected cells. Although IFN-γ significantly reduced the neurite length in uninfected cultures (42.64%; p < 0.001, this inflammatory cytokine reverted the impairment of neurite outgrowth induced by the infection (81.39%. The results suggest a neuroprotective potential response of glia to N. caninum infection under IFN-γ stimulus. This observation contributes to understand the immune mediated mechanisms of neosporosis in CNS

  9. The multifaceted effects of agmatine on functional recovery after spinal cord injury through Modulations of BMP-2/4/7 expressions in neurons and glial cells.

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    Yu Mi Park

    Full Text Available Presently, few treatments for spinal cord injury (SCI are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm, a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm(2 weight for 1 min at thoracic vertebra (Th 9 segment. Mice that received an intraperitoneal (i.p. injection of Agm (100 mg/kg/day within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following

  10. Glutamate activates c-fos in glial cells via a novel mechanism involving the glutamate receptor subtype mGlu5 and the transcriptional repressor DREAM.

    Science.gov (United States)

    Edling, Ylva; Ingelman-Sundberg, Magnus; Simi, Anastasia

    2007-02-01

    Activation of c-fos in brain is related to coupling of neuronal activity to gene expression, but also to pathological conditions such as seizures or excitotoxicity-induced cell death. Glutamate activates c-fos in neurons through the calcium-dependent phosphorylation of CREB by ERK and/or CaMKIV kinase pathways downstream NMDA-receptors. In glial cells, however, the activation of c-fos by glutamate is poorly understood. Because glial cells actively modulate neuronal excitability and the brain's response to injury, we studied the mechanisms by which glutamate activates c-fos in rat cortical glial cells. Glutamate potently induced c-fos mRNA in a calcium-dependent manner, as demonstrated by using the calcium chelator BAPTA-AM. Glutamate-induced c-fos mRNA expression was not sensitive to inhibitors of ERK, p38(MAPK), or CaMK pathways, indicating that glial c-fos is activated by a distinct mechanism. Thapsigargin abolished the glutamate effect on c-fos mRNA, indicating ER calcium mobilization. Additionally, glutamate induction of c-fos mRNA was sensitive to the mGluR5 antagonist MPEP but not the NMDA-R antagonist MK-801. In luciferase reporter assays, DRE, which actively represses c-fos by binding the calcium-binding transcriptional repressor DREAM, was activated by glutamate, whereas SRE and CRE were not. Finally, glutamate caused the nuclear export of DREAM in astrocytes, and transfection of astrocytes with a mutant variant of DREAM that constitutively binds DNA inhibited glutamate-induced c-Fos expression. These findings are in sharp contrast to the mechanism described in neurons and suggest a novel pathway activated by glutamate in glial cells that employs mGluR5, ER calcium, and the derepression of c-fos at the DRE. PMID:17120244

  11. Combination of basic fibroblast growth factor and epidermal growth factor enhances proliferation and neuronal/glial differential of postnatal human enteric neurosphere cells in vitro.

    Science.gov (United States)

    Pan, Wei-Kang; Yu, Hui; Wu, A-Li; Gao, Ya; Zheng, Bai-Jun; Li, Peng; Yang, Wei-Li; Huang, Qiang; Wang, Huai-Jie; Ge, Xin

    2016-08-01

    Human enteric neural stem cells (hENSCs) proliferate and differentiate into neurons and glial cells in response to a complex network of neurotrophic factors to form the enteric nervous system. The primary aim of this study was to determine the effect of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on in-vitro expansion and differentiation of postnatal hENSCs-containing enteric neurosphere cells. Enteric neurosphere cells were isolated from rectal polyp specimens of 75 children (age, 1-13 years) and conditioned with bFGF, EGF, bFGF+EGF, or plain culture media. Proliferation of enteric neurosphere cells was examined using the methyl thiazolyl tetrazolium colorimetric assay over 7 days of culture. Fetal bovine serum (10%) was added to induce the differentiation of parental enteric neurosphere cells, and differentiated offspring cells were immunophenotyped against p75 neutrophin receptor (neural stem cells), peripherin (neuronal cells), and glial fibrillary acidic protein (glial cells). Combining bFGF and EGF significantly improved the proliferation of enteric neurosphere cells compared with bFGF or EGF alone (both P<0.01) throughout 7 days of culture. The addition of bFGF drove a significantly greater proportion of enteric neurosphere cells to differentiate into neuronal cells than that of EGF (P<0.01), whereas addition of EGF resulted in significantly more glial differentiation compared with addition of bFGF (P<0.01). Combining bFGF and EGF drove enteric neurosphere cells to differentiate into neuronal cells in a proportion similar to glial cells. Our results showed that the combination of bFGF and EGF significantly enhanced the proliferation and differentiation of postnatal hENSCs-containing enteric neurosphere cells in vitro. PMID:27306591

  12. Kuldne Mask Tallinnasssssss! / Sergei Zhenovatsh ; interv. Hellar Bergmann

    Index Scriptorium Estoniae

    Zhenovatsh, Sergei

    2008-01-01

    Lavastaja Sergei Zhenovatsh oma Teatrikunsti Stuudiost, noortest näitlejatest, Eestist. Lavastaja on Eestis teatrifestivali "Kuldne mask Eestis" raames. 10.-11. okt. etendus Tallinnas, Salme Kultuurikeskuses Nikolai Gogoli näidend "Mängurid"

  13. Rosenfeld, Bergmann, Dirac and the Invention of Constrained Hamiltonian Dynamics

    OpenAIRE

    Salisbury, D. C.

    2007-01-01

    In a paper appearing in Annalen der Physik in 1930 Leon Rosenfeld invented the first procedure for producing Hamiltonian constraints. He displayed and correctly distinguished the vanishing Hamiltonian generator of time evolution, and the vanishing generator of gauge transformations for general relativity with Dirac electron and electrodynamic field sources. Though he did not do so, had he chosen one of his tetrad fields to be normal to his spacetime foliation, he would have anticipated by alm...

  14. Rosenfeld, Bergmann, Dirac and the Invention of Constrained Hamiltonian Dynamics

    CERN Document Server

    Salisbury, D C

    2008-01-01

    In a paper appearing in Annalen der Physik in 1930 Leon Rosenfeld invented the first procedure for producing Hamiltonian constraints. He displayed and correctly distinguished the vanishing Hamiltonian generator of time evolution, and the vanishing generator of gauge transformations for general relativity with Dirac electron and electrodynamic field sources. Though he did not do so, had he chosen one of his tetrad fields to be normal to his spacetime foliation, he would have anticipated by almost thirty years the general relativisitic Hamiltonian first published by Paul Dirac.

  15. Rosenfeld, Bergmann, Dirac and the Invention of Constrained Hamiltonian Dynamics

    Science.gov (United States)

    Salisbury, D. C.

    2008-09-01

    In a paper appearing in Annalen der Physik in 1930 Leon Rosenfeld invented the first procedure for producing Hamiltonian constraints. He displayed and correctly distinguished the vanishing Hamiltonian generator of time evolution, and the vanishing generator of gauge transformations for general relativity with Dirac electron and electrodynamic field sources. Though he did not do so, had he chosen one of his tetrad fields to be normal to his spacetime foliation, he would have anticipated by almost thirty years the general relativisitic Hamiltonian first published by Paul Dirac.

  16. MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.

    Directory of Open Access Journals (Sweden)

    Hae Kyung Lee

    Full Text Available Glioblastomas (GBM, the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3'-UTR fused to luciferase. Overexpression of a CTGF plasmid lacking the 3'-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors.

  17. Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells

    Science.gov (United States)

    Sariyer, Ilker Kudret; Sariyer, Rahsan; Otte, Jessica; Gordon, Jennifer

    2016-01-01

    Objective PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV), which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs). We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF). SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen. Methods and Results Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins. Conclusions Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral

  18. ER stress upregulated PGE2/IFNγ-induced IL-6 expression and down-regulated iNOS expression in glial cells

    Science.gov (United States)

    Hosoi, Toru; Honda, Miya; Oba, Tatsuya; Ozawa, Koichiro

    2013-12-01

    The disruption of endoplasmic reticulum (ER) function can lead to neurodegenerative disorders, in which inflammation has also been implicated. We investigated the possible correlation between ER stress and immune function using glial cells. We demonstrated that ER stress synergistically enhanced prostaglandin (PG) E2 + interferon (IFN) γ-induced interleukin (IL)-6 production. This effect was mediated through cAMP. Immune-activated glial cells produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress inhibited PGE2 + IFNγ-induced iNOS expression. Similar results were obtained when cells were treated with dbcAMP + IFNγ. Thus, cAMP has a dual effect on immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS expression under ER stress. Therefore, our results suggest a link between ER stress and immune reactions in neurodegenerative diseases.

  19. Comparison of the PET with fluoro-ethyl-tyrosine to perfusion MRI and T1 injected in the exploration of glial tumors: a pilot study

    International Nuclear Information System (INIS)

    Molecular imaging could be used in complement of MRI injected in the initial result of cerebral tumors. This study has for aim to compare the performances of the positron computed tomography with fluoro-ethyl-tyrosine (F.E.T.) with the T1 sequences with gadolinium injection and perfusion MRI in the staging of glial tumors. In spite of the low strength of the series, the cerebral PET shows a good performance in the staging of glial tumors, without being superior to MRI. however, the results seem interesting in view of possible merging to allow targeting at the best, the biopsies, especially for the injuries classified high grade for MRI without contrast after gadolinium injection. (N.C.)

  20. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    OpenAIRE

    Feng Xue; Er-jun Wu; Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Na Han

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive fo...

  1. The saucor, a new stereological tool for analysing the spatial distributions of cells, exemplified by human neocortical neurons and glial cells

    DEFF Research Database (Denmark)

    Stark, Anette K; Gundersen, Hans Jørgen Gottlieb; Gardi, Jonathan Eyal; Pakkenberg, Bente; Hahn, Ute

    2011-01-01

    smaller portion of the volume as the distance to the primary object increases. The experimenter can determine the relation between these volumina as a function of the distance by adjusting the parameters of the window graph, and thus reach a good balance between workload and obtained information...... vertical sections for light microscopy. The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other....

  2. The saucor, a new stereological tool for analysing the spatial distributions of cells, exemplified by human neocortical neurons and glial cells

    DEFF Research Database (Denmark)

    Stark, Anette K.; Gundersen, Hans Jørgen Gottlieb; Gardi, Jonathan Eyal; Pakkenberg, Bente; Hahn, Ute

    is examined and a smaller portion of the volume as the distance to the primary object increases.The experimenter can determine the relation between these volumina as a function of the distance by adjusting the parameters of the window graph, and thus reach a good balance between workload and obtained...... microscopy. The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other....

  3. Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels ▿

    OpenAIRE

    Tribouillard-Tanvier, Déborah; Striebel, James F; Peterson, Karin E.; Chesebro, Bruce

    2009-01-01

    Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage initiated by other processes. In the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected C57BL/10 mouse brains, we observed e...

  4. Gfap-positive radial glial cells are an essential progenitor population for later-born neurons and glia in the zebrafish spinal cord.

    Science.gov (United States)

    Johnson, Kimberly; Barragan, Jessica; Bashiruddin, Sarah; Smith, Cody J; Tyrrell, Chelsea; Parsons, Michael J; Doris, Rosemarie; Kucenas, Sarah; Downes, Gerald B; Velez, Carla M; Schneider, Caitlin; Sakai, Catalina; Pathak, Narendra; Anderson, Katrina; Stein, Rachael; Devoto, Stephen H; Mumm, Jeff S; Barresi, Michael J F

    2016-07-01

    Radial glial cells are presumptive neural stem cells (NSCs) in the developing nervous system. The direct requirement of radial glia for the generation of a diverse array of neuronal and glial subtypes, however, has not been tested. We employed two novel transgenic zebrafish lines and endogenous markers of NSCs and radial glia to show for the first time that radial glia are essential for neurogenesis during development. By using the gfap promoter to drive expression of nuclear localized mCherry we discerned two distinct radial glial-derived cell types: a major nestin+/Sox2+ subtype with strong gfap promoter activity and a minor Sox2+ subtype lacking this activity. Fate mapping studies in this line indicate that gfap+ radial glia generate later-born CoSA interneurons, secondary motorneurons, and oligodendroglia. In another transgenic line using the gfap promoter-driven expression of the nitroreductase enzyme, we induced cell autonomous ablation of gfap+ radial glia and observed a reduction in their specific derived lineages, but not Blbp+ and Sox2+/gfap-negative NSCs, which were retained and expanded at later larval stages. Moreover, we provide evidence supporting classical roles of radial glial in axon patterning, blood-brain barrier formation, and locomotion. Our results suggest that gfap+ radial glia represent the major NSC during late neurogenesis for specific lineages, and possess diverse roles to sustain the structure and function of the spinal cord. These new tools will both corroborate the predicted roles of astroglia and reveal novel roles related to development, physiology, and regeneration in the vertebrate nervous system. GLIA 2016;64:1170-1189. PMID:27100776

  5. Lesion-dependent regulation of transgene expression in the rat brain using a human glial fibrillary acidic protein-lentiviral vector.

    OpenAIRE

    Jakobsson, Johan; Georgievska, Biljana; Ericson, Cecilia; Lundberg, Cecilia

    2004-01-01

    The ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline-regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin-induced lesions we investigated ...

  6. Cell death/proliferation and alterations in glial morphology contribute to changes in diffusivity in the rat hippocampus after hypoxia–ischemia

    OpenAIRE

    Anderova, Miroslava; Vorisek, Ivan; Pivonkova, Helena; Benesova, Jana; Vargova, Lydia; Cicanic, Michal; Chvatal, Alexandr; Sykova, Eva

    2010-01-01

    To understand the structural alterations that underlie early and late changes in hippocampal diffusivity after hypoxia/ischemia (H/I), the changes in apparent diffusion coefficient of water (ADCW) were studied in 8-week-old rats after H/I using diffusion-weighted magnetic resonance imaging (DW-MRI). In the hippocampal CA1 region, ADCW analyses were performed during 6 months of reperfusion and compared with alterations in cell number/cell-type composition, glial morphology, and extracellular s...

  7. CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells

    OpenAIRE

    Rhee, Kun Do; Nusinowitz, Steven; Chao, Kevin; Yu, Fei; Bok, Dean; Yang, Xian-Jie

    2013-01-01

    The cytokine CNTF has been approved by the FDA as a neuroprotective treatment for major retinal degenerative diseases. However, the mechanism of CNTF-triggered protection and CNTF-responsive cells in the retina remains unknown. Using molecular genetic analyses in a retinal degeneration mouse model, we identify the Müller glial cell as the direct initial target of exogenous CNTF signals. We provide evidence that CNTF signals stimulate a Müller glia and photoreceptor intercellular signaling loo...

  8. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications

    International Nuclear Information System (INIS)

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane–polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane–polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. - Highlights: • Polyurethane–polylactide blends exhibit different characteristics from pure polymers. • Pure PU and PLA negatively influence on morphology of glial and mesenchymal cells. • PU/PLA blend was neutral for glial and mesenchymal cell proliferation and morphology

  9. Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy

    OpenAIRE

    Kim, Kijeong; Shin, Mal-Soon; Cho, Han-Sam; Kim, Young-Pyo

    2014-01-01

    Periventricular leukomalacia (PVL) is a common white matter lesion affecting the neonatal brain. PVL is closely associated with cerebral palsy (CP) and characterized by increase in the number of astrocytes, which can be detected by positivity for glial fibrillary acidic protein (GFAP). Change in myelin basic protein (MBP) is an early sign of white matter abnormality. Maternal or placental infection can damage the neonatal brain. In the present study, we investigated the effects of treadmill w...

  10. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications

    Energy Technology Data Exchange (ETDEWEB)

    Grzesiak, Jakub, E-mail: grzesiak.kuba@gmail.com [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Marycz, Krzysztof [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Szarek, Dariusz [Department of Neurosurgery, Lower Silesia Specialist Hospital of T. Marciniak, Emergency Medicine Center, Traugutta 116, 50-420 Wroclaw (Poland); Bednarz, Paulina [State Higher Vocational School in Tarnów, Mickiewicza 8, 33-100 Tarnów (Poland); Laska, Jadwiga [AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Mickiewicza 30, 30-059 Kraków (Poland)

    2015-07-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane–polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane–polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. - Highlights: • Polyurethane–polylactide blends exhibit different characteristics from pure polymers. • Pure PU and PLA negatively influence on morphology of glial and mesenchymal cells. • PU/PLA blend was neutral for glial and mesenchymal cell proliferation and morphology.

  11. PARP1 activation/expression modulates regional-specific neuronal and glial responses to seizure in a hemodynamic-independent manner

    OpenAIRE

    Kim, J-E; Kim, Y-J; Kim, J.Y.; Kang, T-C

    2014-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) plays a regulatory role in apoptosis, necrosis and other cellular processes after injury. Status epilepticus (SE) induces neuronal and astroglial death that show regional-specific patterns in the rat hippocampus and piriform cortex (PC). Thus, we investigated whether PARP1 regulates the differential neuronal/glial responses to pilocarpine (PILO)-induced SE in the distinct brain regions. In the present study, both CA1 and CA3 neurons showed PARP1 hyperacti...

  12. Human teratomas express differentiated neural antigens. An immunohistochemical study with anti-neurofilament, anti-glial filament, and anti-myelin basic protein monoclonal antibodies.

    OpenAIRE

    Trojanowski, J Q.; Hickey, W. F.

    1984-01-01

    Monoclonal antibodies specific for neurofilament proteins, glial filament protein, or myelin basic protein were used with immunohistochemistry for evaluation of a series of 14 human benign and malignant teratomas for the presence of these neural specific antigens. The results indicate that human teratomas can express all of these neural antigens, reflecting the presence of differentiated neurons, astrocytes, and oligodendroglia, respectively. Although the tumors were selected because neural t...

  13. Stromal derived factor-1α in hippocampus radial glial cells in vitro regulates the migration of neural progenitor cells.

    Science.gov (United States)

    Ding, Hui; Jin, Guo-Hua; Zou, Lin-Qing; Zhang, Xiao-Qing; Li, Hao-Ming; Tao, Xue-Lei; Zhang, Xin-Hua; Qin, Jian-Bing; Tian, Mei-Ling

    2015-06-01

    Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries. PMID:25604551

  14. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    Directory of Open Access Journals (Sweden)

    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  15. Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes.

    Directory of Open Access Journals (Sweden)

    Ashley S Pawlisz

    2011-10-01

    Full Text Available Radial glial cells (RGCs are distinctive neural stem cells with an extraordinary slender bipolar morphology and dual functions as precursors and migration scaffolds for cortical neurons. Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophin/dystroglycan glycoprotein complex (DGC. A direct interaction between Nde1 and utrophin/dystrophin allows for the assembly of a multi-protein complex that links the cytoskeleton to the extracellular matrix of RGCs to stabilize their lateral membrane, cell-cell adhesion, and radial morphology. Lis1-Nde1 mutations destabilized the DGC and resulted in deformed, disjointed RGCs and disrupted basal lamina. Besides impaired RGC self-renewal and neuronal migration arrests, Lis1-Nde1 deficiencies also led to neuronal over-migration. Additional to phenotypic resemblances of Lis1-Nde1 with DGC, strong synergistic interactions were found between Nde1 and dystroglycan in RGCs. As functional insufficiencies of LIS1, NDE1, and dystroglycan all cause lissencephaly syndromes, our data demonstrated that a three-dimensional regulation of RGC's cytoarchitecture by the Lis1-Nde1-DGC complex determines the number and spatial organization of cortical neurons as well as the size and shape of the cerebral cortex.

  16. EXPRESSION OF NESTIN AND GLIAL FIBRILLARY ACIDIC PROTEIN IN DIFFERENT PERIOD AFTER SPINAL INJURY IN ADULT RATS

    Institute of Scientific and Technical Information of China (English)

    屈建强; 贺西京; 杨平林; 师蔚; 李浩鹏; 兰宾尚; 袁普卫; 王国毓

    2004-01-01

    Objective To study the expression of Nestin and glial fibrillary acidic protein (GFAP) in different period after spinal injury in adult rats. Methods Animal moels were created by artery clamp. Expression of Nestin and GFAP in different period (1,3,5days;1-8 weeks) and different area(injury locus and its surrounding tissue ) after spinal injury were observed pathologicaly using immunofluorescence and LeicaQ500IW imaging processing system. Results There was expression of Nestin and GFAP in injured area 1 day after injury.The expression increased not only in in injured area but its sourrounding 3-7 days later and gradually got to peak value. As the time went on, expression of Nestin and GFAP dereased. Conclusion Spinal injury can induce the expression of Nestin. Nerve stem cell has response to spinal injury. There is positive correlation between expression of Nestin and hyperplasia of reactivity astrocyte. Nerve stem cell maybe invovled in the repair of central nervous system (CNS).

  17. [Activity of glial cells in the olfactory bulb of Niemann-Pick disease type C1 mice].

    Science.gov (United States)

    Yan, Xin; Qiao, Liang; Yang, En-Hui; Lin, Jun-Tang

    2016-04-25

    To study the pathological mechanisms of Niemann-Pick disease type C1, we observed the changes of activation of glial cells in the olfactory bulb of Npc1 mutant (Npc1(-/-)) mice. The genomic DNA was extracted from mouse tails for genotyping by PCR. Immunofluorescent histochemistry was performed to examine the activation of microglia and astrocytes in the olfactory bulb of Npc1(-/-) mice on postnatal day 30. NeuN, phosphorylated neurofilament (NF), Doublecortin (DCX), CD68 and GFAP were detected by Western blot. The results showed that Npc1 gene mutation strongly increased the activation of astrocytes and microglia in olfactory bulb associated with increased protein levels of CD68 and GFAP. Furthermore, the expression of phosphorylated NF was also significantly increased in the olfactory bulb of Npc1(-/-) mice compared with that in Npc1(+/+) mice. However, DCX expression was significantly reduced. The above results suggest that there are some early changes in the olfactory bulb of Npc1(-/-) mice. PMID:27108900

  18. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

    Directory of Open Access Journals (Sweden)

    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  19. Sympathetic Innervation Induced in Engrafted Engineered Cardiomyocyte Sheets by Glial Cell Line Derived Neurotrophic Factor In Vivo

    Directory of Open Access Journals (Sweden)

    Xian-ming Fu

    2013-01-01

    Full Text Available The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue. However, this strategy has been hampered by lack of functional integration of grafts with native myocardium. Autonomic innervation may be crucial for grafts to function properly with host myocardium. In this study, we explored the feasibility of in vivo induction of autonomic innervation to engineered myocardial tissue using genetic modulation by adenovirus encoding glial cell line derived neurotrophic factor (GDNF. GFP-transgene (control group or GDNF overexpressing (GDNF group engineered cardiomyocyte sheets were transplanted on cryoinjured hearts in rats. Nerve fibers in the grafts were examined by immunohistochemistry at 1, 2, and 4 weeks postoperatively. Growth associated protein-43 positive growing nerves and tyrosine hydroxylase positive sympathetic nerves were first detected in the grafts at 2 weeks postoperatively in control group and 1 week in GDNF group. The densities of growing nerve and sympathetic nerve in grafts were significantly increased in GDNF group. No choline acetyltransferase immunopositive parasympathetic nerves were observed in grafts. In conclusion, sympathetic innervation could be effectively induced into engrafted engineered cardiomyocyte sheets using GDNF.

  20. The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Gokhan Akkoyunlu

    2010-11-01

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN. Docosahexaenoic acid (DHA is the major polyunsaturated fatty acid (PUFA in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF and neurturin (NTN are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA, MPTP-induced (MPTP, MPTP-induced+DHA-treated (MPTP+DHA groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases.

  1. Synchronized Dual Pulse Gastric Electrical Stimulation Induces Activation of Enteric Glial Cells in Rats with Diabetic Gastroparesis

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2014-01-01

    Full Text Available Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7–14-day diabetes and 56–63-day diabetes before and after stimulation and the age-matched control groups. SGES-60 mins and SGES-7 days (60 mins/day were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1 Gastric emptying was accelerated in 7–14-day diabetes and delayed in 56–63-day diabetes. (2 The S100B expression in 56–63-day diabetes decreased and the ultrastructure changed. (3 The age-associated loss of EGC was observed in 56–63-day control group. (4 SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5 The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60 mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation.

  2. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    International Nuclear Information System (INIS)

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial (Ν/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  3. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  4. The Neuro-Protective Effect of the Methanolic Extract of Perilla frutescens var. japonicaand Rosmarinic Acid against H₂O₂-Induced Oxidative Stress in C6 Glial Cells.

    Science.gov (United States)

    Lee, Ah Young; Wu, Ting Ting; Hwang, Bo Ra; Lee, Jaemin; Lee, Myoung-Hee; Lee, Sanghyun; Cho, Eun Ju

    2016-05-01

    Neurodegenerative diseases are often associated with oxidative damage in neuronal cells. This study was conducted to investigate the neuro-protective effect of methanolic (MeOH) extract of Perilla frutescens var. japonica and its one of the major compounds, rosmarinic acid, under oxidative stress induced by hydrogen peroxide (H₂O₂) in C6 glial cells. Exposure of C6 glial cells to H₂O₂ enhanced oxidative damage as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and thiobarbituric acid-reactive substance assays. The MeOH extract and rosmarinic acid prevented oxidative stress by increasing cell viability and inhibiting cellular lipid peroxidation. In addition, the MeOH extract and rosmarinic acid reduced H₂O₂-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcriptional level. Moreover, iNOS and COX-2 protein expression was down-regulated in H₂O₂-indcued C6 glial cells treated with the MeOH extract and rosmarinic acid. These findings suggest that P. frutescens var. japonica and rosmarinic acid could prevent the progression of neurodegenerative diseases through attenuation of neuronal oxidative stress. PMID:27133263

  5. Protective effect of naringin on 3-nitropropionic acid-induced neurodegeneration through the modulation of matrix metalloproteinases and glial fibrillary acidic protein.

    Science.gov (United States)

    Gopinath, Kulasekaran; Sudhandiran, Ganapasam

    2016-01-01

    Naringin (4',5,7-trihydroxy-flavonone-7-rhamnoglucoside), a flavonone present in grapefruit, has recently been reported to protect against neurodegeration, induced with 3-nitropropionic acid (3-NP), through its antioxidant, anti-inflammatory, and antiapoptotic properties. This study used a rat model of 3-NP-induced neurodegeneration to investigate the neuroprotective effects of naringin exerted by modulating the expression of matrix metalloproteinases and glial fibrillary acidic protein. Neurodegeneration was induced with 3-NP (10 mg/kg body mass, by intraperitoneal injection) once a day for 2 weeks, and induced rats were treated with naringin (80 mg/kg body mass, by oral gavage, once a day for 2 weeks). Naringin ameliorated the motor abnormalities caused by 3-NP, and reduced blood-brain barrier dysfunction by decreasing the expression of matrix metalloproteinases 2 and 9, along with increasing the expression of the tissue inhibitors of metalloproteinases 1 and 2 in 3-NP-induced rats. Further, naringin reduced 3-NP-induced neuroinflammation by decreasing the expression of nuclear factor-kappa B and glial fibrillary acidic protein. Thus, naringin exerts protective effects against 3-NP-induced neurodegeneration by ameliorating the expressions of matrix metalloproteinases and glial fibrillary acidic protein. PMID:26544788

  6. The Intricate Expression of CC Chemokines in Glial Tumors: Evidence for Involvement of CCL2 and CCL5 but Not CCL11

    Directory of Open Access Journals (Sweden)

    Mozhgan Moogooei

    2015-12-01

    Full Text Available Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 andCCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, theCCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment.

  7. The Intricate Expression of CC Chemokines in Glial Tumors: Evidence for Involvement of CCL2 and CCL5 but Not CCL11.

    Science.gov (United States)

    Moogooei, Mozhgan; Shamaei, Masoud; Khorramdelazad, Hossein; Fattahpour, Shirin; Seyedmehdi, Seyed Mohammad; Moogooei, Maryam; Hassanshahi, Gholamhossein; Kalantari Khandani, Behjat

    2015-12-01

    Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 and CCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, the CCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment. PMID:26749234

  8. The role of glial-specific Kir4.1 in normal and pathological states of the CNS.

    Science.gov (United States)

    Nwaobi, Sinifunanya E; Cuddapah, Vishnu A; Patterson, Kelsey C; Randolph, Anita C; Olsen, Michelle L

    2016-07-01

    Kir4.1 is an inwardly rectifying K(+) channel expressed exclusively in glial cells in the central nervous system. In glia, Kir4.1 is implicated in several functions including extracellular K(+) homeostasis, maintenance of astrocyte resting membrane potential, cell volume regulation, and facilitation of glutamate uptake. Knockout of Kir4.1 in rodent models leads to severe neurological deficits, including ataxia, seizures, sensorineural deafness, and early postnatal death. Accumulating evidence indicates that Kir4.1 plays an integral role in the central nervous system, prompting many laboratories to study the potential role that Kir4.1 plays in human disease. In this article, we review the growing evidence implicating Kir4.1 in a wide array of neurological disease. Recent literature suggests Kir4.1 dysfunction facilitates neuronal hyperexcitability and may contribute to epilepsy. Genetic screens demonstrate that mutations of KCNJ10, the gene encoding Kir4.1, causes SeSAME/EAST syndrome, which is characterized by early onset seizures, compromised verbal and motor skills, profound cognitive deficits, and salt-wasting. KCNJ10 has also been linked to developmental disorders including autism. Cerebral trauma, ischemia, and inflammation are all associated with decreased astrocytic Kir4.1 current amplitude and astrocytic dysfunction. Additionally, neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis demonstrate loss of Kir4.1. This is particularly exciting in the context of Huntington disease, another neurodegenerative disorder in which restoration of Kir4.1 ameliorated motor deficits, decreased medium spiny neuron hyperexcitability, and extended survival in mouse models. Understanding the expression and regulation of Kir4.1 will be critical in determining if this channel can be exploited for therapeutic benefit. PMID:26961251

  9. Retinal and Optic Nerve Damage is Associated with Early Glial Responses in an Experimental Autoimmune Glaucoma Model.

    Science.gov (United States)

    Noristani, Rozina; Kuehn, Sandra; Stute, Gesa; Reinehr, Sabrina; Stellbogen, Mathias; Dick, H Burkhard; Joachim, Stephanie C

    2016-04-01

    It is well established that the immunization with ocular antigens causes a retinal ganglion cell (RGC) decline, which is accompanied by glia alterations. In this study, the degenerative effects of the immunization with an optic nerve homogenate (ONA) and its purified compound S100 were analyzed on retinas and optic nerves. Since a participation of glia cells in cell death mechanisms is currently discussed, rats were immunized with S100 or ONA. At 14 and 28 days, immune-histological and Western blot analyses were performed to investigate the optic nerve structure (SMI-32), retinal ganglion cells (Brn-3a), apoptosis (cleaved caspase 3, FasL), and glial profile (Iba1, ED1, GFAP, vimentin). Neurofilament dissolution in S100 animals was evident at 14 days (p = 0.047) and increased at 28 days (p = 0.01). ONA optic nerves remained intact at early stages and degenerated later on (p = 0.002). In both groups, RGC loss was detected via immune-histology and Western blot at 28 days (ONA: p = 0.02; S100: p = 0.005). Additionally, more Iba1(+) retinal microglia could be detected at early stages (ONA: p = 0.006; S100: p = 0.028). A slight astrocyte response was detected on Western blots only on ONA retinas (p = 0.01). Hence, the RGC and optic nerve decline was partly antigen dependent, while neuronal loss is paralleled by an early microglial response. PMID:26746422

  10. Extracellular matrix of cultured glial cells: Selective expression of chondroitin 4-sulfate by type-2 astrocytes and their progenitors

    International Nuclear Information System (INIS)

    We have studied the extracellular matrix composition of cultured glial cells by immunocytochemistry with different monoclonal and polyclonal antibodies. Double immunofluorescence experiments and metabolic labeling with [3H]glucosamine performed in different types of cerebellar and cortical cultures showed that bipotential progenitors for type-2 astrocytes and for oligodendrocytes synthesize chondroitin sulfate (CS) and deposit this proteoglycan in their extracellular matrix. The distribution of the various [3H]glucosamine-labeled glycosaminoglycans between the intracellular and the extracellular space was different. CS was present both within the cells and in the culture medium, although in different amounts. Bi-potential progenitors became also O4-positive during their development in vitro. At the stage of O4-positivity they were still stained with antibodies against CS. However, when the progenitor cells were maintained in serum-free medium and differentiated into Gal-C-positive oligodendrocytes, they became CS-negative. In the presence of fetal calf serum in the culture medium, the bipotential progenitors differentiated into GFAP-positive type-2 astrocytes. These cells still expressed CS: their Golgi area and their surface were stained with anti-CS antibodies. Staining with monoclonal antibodies specific for different types of CS (4-sulfate, 6-sulfate, and unsulfated) revealed that both bipotential progenitors and type-2 astrocytes synthesized only chondroitin 4-sulfate. Type-1 astrocytes were negative for both the polyclonal and the monoclonal anti-CS antibodies. Finally, type-2 astrocytes and their progenitors were weakly stained with anti-laminin antibodies and unstained with anti-fibronectin. Type-1 astrocytes were positive for both anti-laminin and anti-fibronectin antibodies and appeared to secrete fibronectin in the extracellular space

  11. Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring

    Directory of Open Access Journals (Sweden)

    Crutcher Keith A

    2001-05-01

    Full Text Available Abstract Background Axons within the mature mammalian central nervous system fail to regenerate following injury, usually resulting in long-lasting motor and sensory deficits. Studies involving transplantation of adult neurons into white matter implicate glial scar-associated factors in regeneration failure. However, these studies cannot distinguish between the effects of these factors and disruption of the spatial organization of cells and molecular factors (disrupted geometry. Since white matter can support or inhibit neurite growth depending on the geometry of the fiber tract, the present study sought to determine whether disrupted geometry is sufficient to inhibit neurite growth. Results Embryonic chick sympathetic neurons were cultured on unfixed longitudinal cryostat sections of mature rat spinal cord or sciatic nerve that had been crushed with forceps ex vivo then immediately frozen to prevent glial scarring. Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions. Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue. In contrast, neurite growth appeared to be unaffected by crushed spinal cord gray matter. Conclusions These observations suggest that glial scar-associated factors are not necessary to block axonal growth at sites of injury. Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

  12. A diphenyl diselenide-supplemented diet and swimming exercise promote neuroprotection, reduced cell apoptosis and glial cell activation in the hypothalamus of old rats.

    Science.gov (United States)

    Leite, Marlon R; Cechella, José L; Pinton, Simone; Nogueira, Cristina W; Zeni, Gilson

    2016-09-01

    Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus. A decrease of B-cell lymphoma 2 (Bcl-2) and procaspase-3 levels as well as an increase of the cleaved PARP/full length PARP ratio (poly (ADP-ribose) polymerase, PARP) and the pJNK/JNK ratio (c-Jun N-terminal kinase, JNK) were observed. The levels of mature brain-derived neurotrophic factor (mBDNF), the pAkt/Akt ratio (also known as protein kinase B) and NeuN (neuronal nuclei), a neuron marker, were decreased in the hypothalamus of old rats. Old rats that received a (PhSe)2-supplemented diet and performed swimming exercise had the hypothalamic levels of Iba-1 and GFAP decreased. The combined treatment also increased the levels of Bcl-2 and procaspase-3 and decreased the ratios of cleaved PARP/full length PARP and pJNK/JNK in old rats. The levels of mBDNF and NeuN, but not the pAkt/Akt ratio, were increased by combined treatment. In conclusion, a (PhSe)2-supplemented diet and swimming exercise promoted neuroprotection in the hypothalamus of old rats, reducing apoptosis and glial cell activation. PMID:27215802

  13. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    Science.gov (United States)

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive. PMID:17901404

  14. Long-term vision and non-vision dominant behavioral deficits in the 2-VO rats are accompanied by time and regional glial activation in the white matter.

    Directory of Open Access Journals (Sweden)

    Xue Song Tian

    Full Text Available The permanent occlusion of common carotid arteries (2-VO in rats has been shown to induce progressive and long-lasting deficits in cognitive performance, however, whether these aberrant behaviors are attributed to visual dysfunction or cognitive impairment and what are the underlying mechanisms, remain controversial. In the present study, vision dominant (Morris water maze and non-vision dominant (voice-cued fear conditioning behavioral tests were assigned to comprehensively evaluate the influence of 2-VO lesion on cognitive behaviors. In the Morris water maze test, escape latencies of 2-VO rats were markedly increased in both hidden and unfixed visible platform tasks, which were accompanied by severe retinal damage. In the voice-cued fear conditioning test, significant reduction in the percentage of freezing behavior was observed at 60 days after 2-VO lesion. Chronic lesion by 2-VO failed to cause noticeable changes in the grey matter, as indicated by intact hippocampal and prefrontal cortical structures, sustained synaptic protein levels and glial cell numbers. In contrast, aberrant arrangement of myelinated axons was observed in the optic tract, but not in the corpus callosum and inner capsule of 2-VO rats. Concurrently, marked astrocyte proliferation and microglia activation in the optic tract occurred at 3 days after 2-VO lesion, and continued for up to 60 days. Differently, robust glial activation was observed in the corpus callosum at 3 days after 2-VO surgery, and then gradually returned to the baseline level at 14 and 60 days. Our study reported for the first time about the effect of 2-VO on the long-term cognitive impairment in the non-vision dominant fear conditioning test, which may be more applicable than the Morris water maze test for assessing 2-VO associated cognitive function. The time and region specific glial activation in the white matter may relate to retinal impairment, even behavioral deficits, in the setting of chronic

  15. The carbonic anhydrase inhibitor methazolamide prevents amyloid beta-induced mitochondrial dysfunction and caspase activation protecting neuronal and glial cells in vitro and in the mouse brain.

    Science.gov (United States)

    Fossati, Silvia; Giannoni, Patrizia; Solesio, Maria E; Cocklin, Sarah L; Cabrera, Erwin; Ghiso, Jorge; Rostagno, Agueda

    2016-02-01

    Mitochondrial dysfunction has been recognized as an early event in Alzheimer's disease (AD) pathology, preceding and inducing neurodegeneration and memory loss. The presence of cytochrome c (CytC) released from the mitochondria into the cytoplasm is often detected after acute or chronic neurodegenerative insults, including AD. The carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) was identified among a library of drugs as an inhibitor of CytC release and proved to be neuroprotective in Huntington's disease and stroke models. Here, using neuronal and glial cell cultures, in addition to an acute model of amyloid beta (Aβ) toxicity, which replicates by intra-hippocampal injection the consequences of interstitial and cellular accumulation of Aβ, we analyzed the effects of MTZ on neuronal and glial degeneration induced by the Alzheimer's amyloid. MTZ prevented DNA fragmentation, CytC release and activation of caspase 9 and caspase 3 induced by Aβ in neuronal and glial cells in culture through the inhibition of mitochondrial hydrogen peroxide production. Moreover, intraperitoneal administration of MTZ prevented neurodegeneration induced by intra-hippocampal Aβ injection in the mouse brain and was effective at reducing caspase 3 activation in neurons and microglia in the area surrounding the injection site. Our results, delineating the molecular mechanism of action of MTZ against Aβ-mediated mitochondrial dysfunction and caspase activation, and demonstrating its efficiency in a model of acute amyloid-mediated toxicity, provide the first combined in vitro and in vivo evidence supporting the potential of a new therapy employing FDA-approved CAIs in AD. PMID:26581638

  16. Administration of activated glial condition medium in the nucleus accumbens extended extinction and intensified reinstatement of methamphetamine-induced conditioned place preference.

    Science.gov (United States)

    Arezoomandan, Reza; Moradi, Marzieh; Attarzadeh-Yazdi, Ghassem; Tomaz, Carlos; Haghparast, Abbas

    2016-07-01

    Methamphetamine (METH) is a psychostimulant drug with significant abuse potential and neurotoxic effects. A high percentage of users relapse to use after detoxification and no effective medication has been developed for treatment of METH addiction. Developing evidences indicated the role of glial cells in drugs abused related phenomena. However, little is known about the role of these cells in the maintenance and reinstatement of METH-seeking behaviors. Therefore, the current study was conducted to clarify the role of glial cells in the maintenance and reinstatement of METH-induced conditioned place preference (CPP) in rats. Astrocyte condition medium (ACM) and neuroglia conditioned medium (NCM) are liquid mediums prepared from primary astrocyte and neuroglia cells. These mediums seem to contain many factors that release by glia cells. CPP was induced by systemic administration of METH (1mg/kg for 5days, s.c.). Following the establishment of CPP, the rats were given daily bilateral injections (0.5μl/side) of either vehicle, ACM or NCM into the nucleus accumbens (NAc) and then were tested for the maintenance and reinstatement. Intra-NAc administration of ACM treated with METH, could extend the extinction period and also, intensified the magnitude of METH reinstatement. Furthermore, intra-accumbal administration of NCM treated with METH notably delayed the extinction period by four days and significantly increased the magnitude of CPP score in the reinstatement phase compared to the post-test phase. Collectively, these findings suggested that activation of glial cells may be involved in the maintenance and reinstatement of METH-seeking behaviors. It provides new evidence that glia cells might be considered as a potential target for the treatment of METH addiction. PMID:27346277

  17. Respuesta de una subpoblación de interneuronas y del transportador glial de glutamato GLT1 en la corteza contralateral a un foco isquémico

    Directory of Open Access Journals (Sweden)

    Adriana M. Medina

    2008-09-01

    Full Text Available Introducción: La isquemia cerebral es una de las formas de lesión cerebral mas frecuentes en el humano. Usualmente los investigadores cuando estudian su fisiopatología se centran en las áreas directamente comprometidas: región del foco, o en las zonas de penumbra, olvidando otros sectores vecinos o no del foco que están conectados con estos sectores de injuria, los cuales pueden estar implicados en algunos de los síntomas que se observan en los pacientes que sufren procesos isquémicos.Objetivo: Evaluar el comportamiento laminar de una subpoblación de interneuronas y de la población glial de la corteza cerebral contralateral al foco isquémico, a través de los marcadores parvalbúmina (PV, que detecta neuronas gabaérgicas y del transportador glial de glutamato GLT1.Materiales y métodos: Se ocluyó la arteria cerebral media derecha en ratas macho adultas, durante 90 minutos, utilizando una sutura intraluminal. Los animales se sacrificaron a las 24 y 72 horas post isquemia. El análisis se hizo en la corteza contralateral al foco, identificando interneuronas PV positivas y la expresión en astrocitos del transportador GLT1.Resultados: Se encontró disminución significativa de la marcación del transportador de glutamato, GLT1, en las capas III y IV de la corteza contralateral al foco isquémico y un aumento en la expresión de PV en las capas II a V comparado con los animales controles.Conclusiones: Los cambios en la expresión de GLT1 pueden proveer un nuevo estado de regulación de glutamato y un patrón diferente de actividad en áreas remotas a un foco isquémico. El aumento en la expresión de PV puede corresponder a un mecanismo adaptativo asociado al incremento de glutamato, por la disminución del transportador, en las envolturas gliales de las sinapsis. Este estudio representa un ejemplo de plasticidad neuronal y glial en zonas remotas al foco isquémico pero conectadas con el mismo.

  18. Glial Cell-Elicited Activation of Brain Microvasculature in Response to Brucella abortus Infection Requires ASC Inflammasome-Dependent IL-1β Production.

    Science.gov (United States)

    Miraglia, M Cruz; Costa Franco, Miriam M; Rodriguez, Ana M; Bellozi, Paula M Q; Ferrari, Carina C; Farias, Maria I; Dennis, Vida A; Barrionuevo, Paula; de Oliveira, Antonio C P; Pitossi, Fernando; Kim, Kwang Sik; Delpino, M Victoria; Oliveira, Sergio Costa; Giambartolomei, Guillermo H

    2016-05-01

    Blood-brain barrier activation and/or dysfunction are a common feature of human neurobrucellosis, but the underlying pathogenic mechanisms are largely unknown. In this article, we describe an immune mechanism for inflammatory activation of human brain microvascular endothelial cells (HBMEC) in response to infection with Brucella abortus Infection of HBMEC with B. abortus induced the secretion of IL-6, IL-8, and MCP-1, and the upregulation of CD54 (ICAM-1), consistent with a state of activation. Culture supernatants (CS) from glial cells (astrocytes and microglia) infected with B. abortus also induced activation of HBMEC, but to a greater extent. Although B. abortus-infected glial cells secreted IL-1β and TNF-α, activation of HBMEC was dependent on IL-1β because CS from B. abortus-infected astrocytes and microglia deficient in caspase-1 and apoptosis-associated speck-like protein containing a CARD failed to induce HBMEC activation. Consistently, treatment of CS with neutralizing anti-IL-1β inhibited HBMEC activation. Both absent in melanoma 2 and Nod-like receptor containing a pyrin domain 3 are partially required for caspase-1 activation and IL-1β secretion, suggesting that multiple apoptosis-associated speck-like protein containing CARD-dependent inflammasomes contribute to IL-1β-induced activation of the brain microvasculature. Inflammasome-mediated IL-1β secretion in glial cells depends on TLR2 and MyD88 adapter-like/TIRAP. Finally, neutrophil and monocyte migration across HBMEC monolayers was increased by CS from Brucella-infected glial cells in an IL-1β-dependent fashion, and the infiltration of neutrophils into the brain parenchyma upon intracranial injection of B. abortus was diminished in the absence of Nod-like receptor containing a pyrin domain 3 and absent in melanoma 2. Our results indicate that innate immunity of the CNS set in motion by B. abortus contributes to the activation of the blood-brain barrier in neurobrucellosis and IL-1β mediates

  19. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

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    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  20. Alternative mRNA Splicing from the Glial Fibrillary Acidic Protein (GFAP) Gene Generates Isoforms with Distinct Subcellular mRNA Localization Patterns in Astrocytes

    DEFF Research Database (Denmark)

    Thomsen, Rune; Daugaard, Tina Fuglsang; Holm, Ida E;

    2013-01-01

    The intermediate filament network of astrocytes includes Glial fibrillary acidic protein (Gfap) as a major component. Gfap mRNA is alternatively spliced resulting in generation of different protein isoforms where Gfapa is the most predominant isoform. The Gfapd isoform is expressed in proliferating...... mRNA localization patterns were dependent on the different 39-exon sequences included in Gfapd and Gfapa mRNA. The presented results show that alternative Gfap mRNA splicing results in isoform-specific mRNA localization patterns with resulting different local mRNA concentration ratios which have...

  1. Preparation and evaluation of ethyl [18F]fluoroacetate as a proradiotracer of [18F]fluoroacetate for the measurement of glial metabolism by PET

    International Nuclear Information System (INIS)

    Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [18F]fluoroacetate ([18F]EFA), which is [18F]fluoroacetate ([18F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [18F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1-14C]fluoroacetate ([14C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [14C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [14C]EFA was measured. Biodistribution studies of [18F]EFA in ddY mice were carried out and compared with [18F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [18F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [18F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6±3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [14C]EFA was 3.8 times higher than that of sodium [1-14C]fluoroacetate. [14C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [14C]EFA was stable only in primate plasma

  2. Severity and timing: How prenatal stress exposure affects glial developmental, emotional behavioural and plasma neurosteroid responses in guinea pig offspring.

    Science.gov (United States)

    Bennett, Greer A; Palliser, Hannah K; Walker, David; Hirst, Jonathan

    2016-08-01

    significantly reduced in GA35-65 and GA 60-65 stress exposed fetuses with those in the GA35-65 stress group remaining reduced by juvenility. This study has shown the effects of differing levels of prenatal stress severity and timing on glial development, emotional behaviour and plasma allopregnanolone concentrations in offspring. PMID:27155257

  3. The new glial model.

    Directory of Open Access Journals (Sweden)

    Francesco Amato

    2012-09-01

    Full Text Available The management of clinical pain
is a major challenge in health care
and basic research.
 New protein structures involved in the transduction of pain such as thermal receptors “Transient Receptor Potential” (TRP, receptors of potential transition, that are non-selective cation channels, have been identified in recent studies. The inflammatory process lowers the threshold for activation of receptors TRP, which is normally active at higher body temperatures than the baseline. Recent studies have shown that the TRPV1 plays a role in the activation of the glia cord in the presence of nociceptive, inflammatory and neuropathic pain, through the activation of an action potential responsible for the release of neurotransmitters such as glutamate and CGRP in the dorsal horn.
 So, this process activates and supports the mechanism of chronic pain. A greater appreciation of the role 
of various mediators or mechanisms that activate microglia could help bring new therapeutic targets
in the future and new efforts
 to improve the treatment
 of severe symptoms of chronic pain.

  4. Glial Synapses Found Plastic

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Traditionally regarded as merely padding and supportive, glia, small cells that dramatically outnumber their larger neighbors, neurons, may play an essential role in information processing in the brain.

  5. Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.

    Science.gov (United States)

    Boneva, S K; Groß, T R; Schlecht, A; Schmitt, S I; Sippl, C; Jägle, H; Volz, C; Neueder, A; Tamm, E R; Braunger, B M

    2016-06-14

    Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina. PMID:27026593

  6. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

    Directory of Open Access Journals (Sweden)

    Heikki Kiiski

    2013-05-01

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  7. Ethanol intake-induced apoptosis in glial cells and axonal disorders in the cerebellar white matter of UChA rats (voluntary ethanol consumers).

    Science.gov (United States)

    Martinez, Marcelo; Sauce, Rafael; Oliveira, Suelen Alves; de Almeida Chuffa, Luiz Gustavo; Stefanini, Maíra Aparecida; Lizarte Neto, Fermino Sanches; Takase, Luiz Fernando; Tirapelli, Luiz Fernando; Martinez, Francisco Eduardo

    2015-08-01

    Ethanol intake may cause alterations in cellular metabolism altering motricity, learning and cognition. The cerebellum is one of the most susceptible organs to ethanol-related disorders during development, and is associated with oxidative stress-induced apoptosis being crucial for pathogenic consequences. The UChA variety is a special strain of Wistar rat genetically selected and represents a rare model for the studies related to genetic, biochemical, physiological, nutritional, and pharmacological effects of ethanol. We evaluated the structure and apoptosis in the cerebellar white matter of UChA rats. There were two groups of 09 rats: a control group that did not consume ethanol, and an experimental group of UChA rats that consumed ethanol at 10% (v/v) (<2 g ethanol/kg body weight/day). At 120 days old, rats were anaesthetized followed by decapitation, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for Caspase-3 and XIAP and transmission electron microscopy (TEM). The UChA group showed more glial cells immunoreactive for caspase-3 and less for XIAP than control group. Alcohol consumption affected myelin integrity. Severe ultrastructural damages in UChA group were observed such as disruption of the myelin sheath, disorganization and deformation of its components, and an increase in the interaxonal spaces. In conclusion, our data demonstrated that ethanol induced apoptosis in the glial cells and promoted an intense change in the myelin sheath of UChA rats, which may cause functional disorders. PMID:26072102

  8. Bacopa monniera (CDRI-08 Upregulates the Expression of Neuronal and Glial Plasticity Markers in the Brain of Scopolamine Induced Amnesic Mice

    Directory of Open Access Journals (Sweden)

    Arpita Konar

    2015-01-01

    Full Text Available Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08 on the expression of key neuronal (BDNF and Arc and glial (GFAP plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders.

  9. Thermomineral water promotes axonal sprouting but does not reduce glial scar formation in a mouse model of spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Dubravka Aleksi; Milan Aksi; Nevena Divac; Vidosava Radonji; Branislav Filipovi; Igor Jakovevski

    2014-01-01

    Thermomineral water from the Atomic Spa Gornja Trepča has been used for a century in the treatment of neurologic disease. The thermomineral water contains microelements, including lithium and magnesium, which show neural regeneration-promoting effects after central nervous system injury. In this study, we investigated the effects of oral intake of thermomineral water from the Atomic Spa Gornja Trepča on nerve regeneration in a 3-month-old mouse model of spinal cord injury. The mice receiving oral intake of thermomineral water showed better locomo-tor recovery than those without administration of thermomineral water at 8 and 12 weeks after lower thoracic spinal cord compression. At 12 weeks after injury, sprouting of catecholaminergic axons was better in mice that drank thermomineral water than in those without administration of thermomineral water, but there was no difference in glial reaction to injury between mice with and without administration of thermomineral water. These ifndings suggest that thermomineral water can promote the nerve regeneration but cannot reduce glial scar formation in a mouse model of spinal cord injury.

  10. 大鼠脊髓胶质瘢痕形成的规律%Formation of glial scar in the rat spinal cord after injury

    Institute of Scientific and Technical Information of China (English)

    黄凯; 盛伟斌

    2012-01-01

    BACKGROUND: After spinal cord injury, the treatment cannot completely solve the problem with the body because glial scarforms and cystic degeneration occurs in the spinal cord tissue. Therefore, it is of great significance to know the regularity of glialscar development.OBJECTIVE: To analyze the spatial distribution, characteristics of axon and time characteristics of glial scar in the rat spinal cordafter experimental spinal cord injury.METHODS: SD rats were divided into control group, 1-day group, 3-day group, 5-day group, 1-week group, 2-week group,4-week group, 6-week group, 8-week group, 10-week group and 12-week group. Allen's weight-drop method was performed toprepare spinal cord injury models in rats expect the control group.RESULTS AND CONCLUSION: At 4 weeks after spinal cord injury, glial scar and smooth cavity wall began to form. Noastrocytes positive for glial fibrillary acidic protein and axons positive for neurofilament protein existed inside the cavity. The glialscar begun to stabilize at 4 weeks after spinal cord injury, and mechanical barriers between the cavity and axon came into being.Thickness of the glial scar no more increased at 10 weeks after spinal cord injury.%背景:脊髓损伤后治疗不理想的原因是脊髓组织的囊变和胶质瘢痕的形成,因此,明确胶质瘢痕的发生发展规律具有重要意义.目的:观察大鼠脊髓损伤后脊髓胶质瘢痕形成的空间分布、时间规律,以及轴突变化特征.方法:采用改良Allen重物坠落法建立SD大鼠脊髓损伤模型,分别于损伤后1 d,3 d,5 d,1周,2周,4周,6周,8周,10周,12周取材.以正常饲养的大鼠作对照.结果与结论:大鼠脊髓损伤后4周开始出现致密瘢痕增生,之后瘢痕厚度平稳下降,至损伤后10周形成光滑的囊腔壁,囊腔内无胶质纤维酸性蛋白阳性星形胶质细胞,损伤区囊腔周围的胶质瘢痕内可见密集肥大的星形胶质细胞,未见神经丝蛋白阳性轴突位于

  11. Secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

    Institute of Scientific and Technical Information of China (English)

    Sanjiang Feng; Minghua Zhuang; Rui Wu

    2012-01-01

    The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7–10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion. Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

  12. The G protein-coupled receptor GPR157 regulates neuronal differentiation of radial glial progenitors through the Gq-IP3 pathway.

    Science.gov (United States)

    Takeo, Yutaka; Kurabayashi, Nobuhiro; Nguyen, Minh Dang; Sanada, Kamon

    2016-01-01

    The ability of radial glial progenitors (RGPs) to generate cortical neurons is determined by local extracellular factors and signaling pathways intrinsic to RGPs. Here we find that GPR157, an orphan G protein-coupled receptor, localizes to RGPs' primary cilia exposed to the cerebrospinal fluid (CSF). GPR157 couples with Gq-class of the heterotrimeric G-proteins and signals through IP3-mediated Ca(2+) cascade. Activation of GPR157-Gq signaling enhances neuronal differentiation of RGPs whereas interfering with GPR157-Gq-IP3 cascade in RGPs suppresses neurogenesis. We also detect the presence of putative ligand(s) for GPR157 in the CSF, and demonstrate the increased ability of the CSF to activate GPR157 at neurogenic phase. Thus, GPR157-Gq signaling at the primary cilia of RGPs is activated by the CSF and contributes to neurogenesis. PMID:27142930

  13. Analysis of gene expression in a human-derived glial cell line exposed to 2.45 GHz continuous radiofrequency electromagnetic fields

    International Nuclear Information System (INIS)

    The increasing use of mobile phones has aroused public concern regarding the potential health risks of radiofrequency (RF) fields. We investigated the effects of exposure to RF fields (2.45 GHz, continuous wave) at specific absorption rate (SAR) of 1, 5, and 10 W/kg for 1, 4, and 24 h on gene expression in a normal human glial cell line, SVGp12, using DNA microarray. Microarray analysis revealed 23 assigned gene spots and 5 non-assigned gene spots as prospective altered gene spots. Twenty-two genes out of the 23 assigned gene spots were further analyzed by reverse transcription-polymerase chain reaction to validate the results of microarray, and no significant alterations in gene expression were observed. Under the experimental conditions used in this study, we found no evidence that exposure to RF fields affected gene expression in SVGp12 cells. (author)

  14. Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization.

    Science.gov (United States)

    Durham, Paul L

    2016-08-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

  15. Preparation and evaluation of ethyl [{sup 18}F]fluoroacetate as a proradiotracer of [{sup 18}F]fluoroacetate for the measurement of glial metabolism by PET

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Sun, Li-Quan [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)], E-mail: ykiyono@u-fukui.ac.jp; Okazawa, Hidehiko; Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kawashima, Hidekazu [Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Welch, Michael J. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)

    2009-02-15

    Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [{sup 18}F]fluoroacetate ([{sup 18}F]EFA), which is [{sup 18}F]fluoroacetate ([{sup 18}F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [{sup 18}F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1-{sup 14}C]fluoroacetate ([{sup 14}C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [{sup 14}C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [{sup 14}C]EFA was measured. Biodistribution studies of [{sup 18}F]EFA in ddY mice were carried out and compared with [{sup 18}F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [{sup 18}F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [{sup 18}F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6{+-}3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [{sup 14}C]EFA was 3.8 times higher than that of sodium [1-{sup 14}C]fluoroacetate. [{sup 14}C]EFA was hydrolyzed rapidly in rat brains. In stability

  16. Co-transplantation of controlled release glial cell line-derived neurotrophic factor and bone marrow mesenchymal stem cells-derived neuron-like cells reduces glial scars after spinal cord injury%控释神经营养因子与细胞移植减少损伤脊髓的胶质瘢痕

    Institute of Scientific and Technical Information of China (English)

    刘晓刚; 邓宇斌; 蔡辉; 张新鹏; 马郁琳; 魏可心

    2013-01-01

    BACKGROUND:Previous studies have demonstrated that transplantation of control ed release glial cellline-derived neurotrophic factor and bone marrow mesenchymal stem cells-derived neuron-like cells can effectively promote the motor function and sensory function recovery of rhesus monkeys with spinal cord injury. OBJECTIVE:To validate whether co-transplantation of control ed release glial cellline-derived neurotrophic factor and bone marrow mesenchymal stem cells-derived neuron-like cells exhibits better protective effects on spinal cord glial scar of rhesus monkeys with spinal cord injury than celltransplantation alone. METHODS:Twelve rhesus monkeys were col ected to prepare animal models of acute severe spinal cord injury using modified Al en’s method, and then randomly divided into three groups:experimental group, co-transplantation of control ed release glial cellline-derived neurotrophic factor and bone marrow mesenchymal stem cells-derived neuron-like cells;control group, simple transplantation of bone marrow mesenchymal stem cells-derived neuron-like cells;blank control group, PBS. After 5 months, paraffin specimens of the spinal cord were made for detection of morphological and compositional characteristics of glial scar, regeneration of nerve fibers in the scar, glial scar area, and average absorbance of glial fibril ary acidic protein. RESULTS AND CONCLUSION:Glial scar in the injured spinal cord was composed of astrocytes and histocytes. Less spinal cord glial scar area and lower absorbance value could be observed in the experimental and control groups as compared with the blank control group (P  目的:观察控释胶质细胞源性神经营养因子联合骨髓间充质干细胞源神经元样细胞移植抑制猴脊髓损伤后胶质瘢痕形成的作用是否优于单纯细胞移植。  方法:取12只恒河猴,采用改良Al en氏法制作急性重度脊髓损伤模型,随机数字表法分为3组,实验组以控释胶质细胞源

  17. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

    Science.gov (United States)

    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. PMID:26896832

  18. Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

    Science.gov (United States)

    Y Ho, E C; Truccolo, Wilson

    2016-10-01

    How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under

  19. Relationships between radial glial progenitors and 5-HT neurons in the paraventricular organ of adult zebrafish - potential effects of serotonin on adult neurogenesis.

    Science.gov (United States)

    Pérez, María Rita; Pellegrini, Elisabeth; Cano-Nicolau, Joel; Gueguen, Marie-Madeleine; Menouer-Le Guillou, Dounia; Merot, Yohann; Vaillant, Colette; Somoza, Gustavo M; Kah, Olivier

    2013-11-01

    In non-mammalian vertebrates, serotonin (5-HT)-producing neurons exist in the paraventricular organ (PVO), a diencephalic structure containing cerebrospinal fluid (CSF)-contacting neurons exhibiting 5-HT or dopamine (DA) immunoreactivity. Because the brain of the adult teleost is known for its neurogenic activity supported, for a large part, by radial glial progenitors, this study addresses the origin of newborn 5-HT neurons in the hypothalamus of adult zebrafish. In this species, the PVO exhibits numerous radial glial cells (RGCs) whose somata are located at a certain distance from the ventricle. To study relationships between RGCs and 5-HT CSF-contacting neurons, we performed 5-HT immunohistochemistry in transgenic tg(cyp19a1b-GFP) zebrafish in which RGCs are labelled with GFP under the control of the cyp19a1b promoter. We show that the somata of the 5-HT neurons are located closer to the ventricle than those of RGCs. RGCs extend towards the ventricle cytoplasmic processes that form a continuous barrier along the ventricular surface. In turn, 5-HT neurons contact the CSF via processes that cross this barrier through small pores. Further experiments using proliferating cell nuclear antigen or 5-bromo-2'-deoxyuridine indicate that RGCs proliferate and give birth to 5-HT neurons migrating centripetally instead of centrifugally as in other brain regions. Furthermore, treatment of adult zebrafish with tryptophan hydroxylase inhibitor causes a significant decrease in the number of proliferating cells in the PVO, but not in the mediobasal hypothalamus. These data point to the PVO as an intriguing region in which 5-HT appears to promote genesis of 5-HT neurons that accumulate along the brain ventricles and contact the CSF. PMID:23981075

  20. First evidence for glial pathology in late life minor depression:S100B is increased in males with minor depression

    Directory of Open Access Journals (Sweden)

    Maryna ePolyakova

    2015-10-01

    Full Text Available Minor depression is diagnosed when a patient suffers from two to four depressive symptoms for at least two weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF, S100B and neuron specific enolase (NSE. 27 subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE. Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index, and degree of white matter hyperintensities (score on Fazekas scale. S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (p=0.10-0.66. NSE correlated with Fazekas score in patients with minor depression (r=0.436, p=0.048 and in the whole sample (r=0.252, p=0.019. S100B correlated with body mass index (r=0.246, p=0.031 and with age in healthy subjects (r=0.345, p=0.002. Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

  1. The high-mobility group box 1 cytokine induces transporter-mediated release of glutamate from glial subcellular particles (gliosomes) prepared from in situ-matured astrocytes.

    Science.gov (United States)

    Bonanno, Giambattista; Raiteri, Luca; Milanese, Marco; Zappettini, Simona; Melloni, Edon; Pedrazzi, Marco; Passalacqua, Mario; Tacchetti, Carlo; Usai, Cesare; Sparatore, Bianca

    2007-01-01

    The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and beta-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-alphaM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several approximately 30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca(2+) and Ca(2+) release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [(3)H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca(2+) concentration, but it was blocked by dl-threo-beta-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine

  2. Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells

    International Nuclear Information System (INIS)

    Previous studies revealed that Mn(II) is accumulated in cultured glial cells to concentrations far above those present in whole brain or in culture medium. The data indicated that Mn(II) moves across the plasma membrane into the cytoplasm by facilitated diffusion or counter-ion transport with Ca(II), then into mitochondria by active transport. The fact that 1-10 microM Mn(II) ions activate brain glutamine synthetase makes important the regulation of Mn(II) transport in the CNS. Since Cu(II) and Zn(II) caused significant changes in the accumulation of Mn(II) by glia, the mechanisms by which these ions alter the uptake and efflux of Mn(II) ions has been investigated systematically under chemically defined conditions. The kinetics of [54MN]-Mn(II) uptake and efflux were determined and compared under four different sets of conditions: no adducts, Cu(II) or Zn(II) added externally, and with cells preloaded with Cu(II) or Zn(II) in the presence and absence of external added metal ions. Zn(II) ions inhibit the initial velocity of Mn(II) uptake, increase total Mn(II) accumulated, but do not alter the rate or extent Mn(II) efflux. Cu(II) ions increase both the initial velocity and the net Mn(II) accumulated by glia, with little effect on rate or extent of Mn(II) efflux. These results predict that increases in Cu(II) or Zn(II) levels may also increase the steady-state levels of Mn(II) in the cytoplasmic fraction of glial cells, which may in turn alter the activity of Mn(II)-sensitive enzymes in this cell compartment

  3. Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wedler, F.C.; Ley, B.W. (Dept. of Molecular Cell Biology, Pennsylvania State University, University Park (USA))

    1990-12-01

    Previous studies revealed that Mn(II) is accumulated in cultured glial cells to concentrations far above those present in whole brain or in culture medium. The data indicated that Mn(II) moves across the plasma membrane into the cytoplasm by facilitated diffusion or counter-ion transport with Ca(II), then into mitochondria by active transport. The fact that 1-10 microM Mn(II) ions activate brain glutamine synthetase makes important the regulation of Mn(II) transport in the CNS. Since Cu(II) and Zn(II) caused significant changes in the accumulation of Mn(II) by glia, the mechanisms by which these ions alter the uptake and efflux of Mn(II) ions has been investigated systematically under chemically defined conditions. The kinetics of (54MN)-Mn(II) uptake and efflux were determined and compared under four different sets of conditions: no adducts, Cu(II) or Zn(II) added externally, and with cells preloaded with Cu(II) or Zn(II) in the presence and absence of external added metal ions. Zn(II) ions inhibit the initial velocity of Mn(II) uptake, increase total Mn(II) accumulated, but do not alter the rate or extent Mn(II) efflux. Cu(II) ions increase both the initial velocity and the net Mn(II) accumulated by glia, with little effect on rate or extent of Mn(II) efflux. These results predict that increases in Cu(II) or Zn(II) levels may also increase the steady-state levels of Mn(II) in the cytoplasmic fraction of glial cells, which may in turn alter the activity of Mn(II)-sensitive enzymes in this cell compartment.

  4. Studies on glial isomeration of lamina cribrosa in rat%大鼠视神经筛板胶质异构的研究

    Institute of Scientific and Technical Information of China (English)

    戴超; 李大庆; 李英; Geoffrey Raisman; 阴正勤

    2013-01-01

    Objective To explore the mechanism of optic nerve damage in glaucoma by study on structure of glial lamina cribrosa(LC) in rats.Methods Experimental study.Albino Swiss(AS) rats were divided into 3 groups.Bilateral eyes of 10 normal rats were employed to be group Ⅰ (right eye) and group Ⅱ (left eye).Group Ⅲ was from the left eyes of 13 rats underwent artificially intraocular hypertension in the right eyes.All rats were perfused and fixed with electronic microscopy fixative (2% paraformaldehyde + 2% glutaraldehyde).Trimmed optic nerves were embedded with resin.Serial 1.5 μm thick 'semithin' sections were cut,either (2 eyes from group Ⅲ) longitudinally,through the optic nerve head(ONH) from the retinal end to the commencement of the optic nerve,or (31 eyes) transversely (cross-sections).Ultrathin sections were cut in the middle of glial LC.The morphological observation of glial LC was obtained by light microscopy and transmission electron microscopy.Bonferroni correction was used to cownteract the multiple comparision of each group.Results Fortified astrocytes formed the main supportive structure of glial LC in all rats,including group Ⅰ,group Ⅱ and group Ⅲ.Astrocytes were ranked as a fan-like radial array,firmly attached ventrally to the sheath of the LC by thick basal processes,but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath.These fortified astrocytes form ventral stout basal end feet,radial array,axon free-'preterminal' layer before terminating in a complex layer of fine interdigitating delicate branches at the dorsal.LC astrocytes were highly and uniformly electron dense throughout all the cell processes.An equally striking feature of the astrocytic processes was their massive cytoskeletal 'strengthening' of longitudinal massed filaments and tubules.Especially,massive filaments accumulated as cytoskeletal cores to form 'scaffold' of fortified astrocytes.There was vulnerable area in the

  5. Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina

    Directory of Open Access Journals (Sweden)

    Bibliowicz Jonathan

    2009-10-01

    Full Text Available Abstract Background The roles of the Hedgehog (Hh pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. Results To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. Conclusion Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS, a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2, and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS

  6. Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats

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    Katagiri Ayano

    2012-03-01

    Full Text Available Abstract Background It has been reported that the P2Y12 receptor (P2Y12R is involved in satellite glial cells (SGCs activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP immunohistochemistries in the trigeminal ganglion (TG in a rat model of unilateral lingual nerve crush (LNC to evaluate role of P2Y12R in SGC in lingual neuropathic pain. Results The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN-IR cells (i.e. neurons in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats

  7. ALS-linked SOD1 in glial cells enhances ß-N-Methylamino L-Alanine (BMAA)-induced toxicity in Drosophila

    Science.gov (United States)

    Islam, Rafique; Zhang, Bing

    2012-01-01

    Environmental factors have been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of environmental agents in ALS remains poorly understood. To this end, we used transgenic fruit flies (Drosophila melanogaster) to explore the interaction between mutant superoxide dismutase 1 (SOD1) and chemicals such as ß-N-methylamino L-alanine (BMAA), the herbicide agent paraquat, and superoxide species. We expressed ALS-linked human SOD1 (hSOD1A4V, and hSOD1G85R), hSOD1wt as well as the Drosophila native SOD1 (dSOD1) in motoneurons (MNs) or in glial cells alone and simultaneously in both types of cells. We then examined the effect of BMAA (3 mM), paraquat (20 mM), and hydrogen peroxide (H2O2, 1%) on the lifespan of SOD1-expressing flies. Our data show that glial expression of mutant and wild type hSOD1s reduces the ability of flies to climb. Further, we show that while all three chemicals significantly shorten the lifespan of flies, mutant SOD1 does not have a significant additional effect on the lifespan of flies fed on paraquat, but further shortens the lifespan of flies fed on H2O2. Finally, we show that BMAA shows a dramatic cell-type specific effect with mutant SOD1. Flies with expression of mutant hSOD1 in MNs survived longer on BMAA compared to control flies. In contrast, BMAA significantly shortened the lifespan of flies expressing mutant hSOD1 in glia. Consistent with a neuronal protection role, flies expressing these mutant hSOD1s in both MNs and glia also lived longer. Hence, our studies reveal a synergistic effect of mutant SOD1 with H2O2 and novel roles for mutant hSOD1s in neurons to reduce BMAA toxicity and in glia to enhance the toxicity of BMAA in flies. PMID:24627764

  8. HIV-1B gp120 genes from one patient with AIDS dementia complex can affect the secretion of tumor necrosis factor and interleukin in glial cells

    Institute of Scientific and Technical Information of China (English)

    YAN Yu-fen; WANG Zhi-yu; PU Shuang-shuang; WEN Hong-ling; HUANG Tao; SONG Yan-yan; XU Hong-zhi; ZHAO Li

    2011-01-01

    Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins,such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β),which play major role in the neuronal death.It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-α by peripheral blood mononuclear cell (PBMC); however,whether the difference of gp120 gene could affect the secretion of TNF-α and IL-1β by glial cells is unknown.The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines.Methods In this study,we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex (ADC).Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120,pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells.Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately.Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree.Compared to the pMIG retrovirus (gp120-negative) or U87 cells,all the gp120-positive recombinant retroviruses induced more TNF-α (P <0.01) and IL-1β (P <0.01).In addition,compared with the L/MIG retrovirus,all the three brain gp120-positive recombinant retroviruses induced less TNF-α (P <0.01) and IL-1β (P <0.01).Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again.The more important is that difference of HIV-1 gp120,especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1β,which might supply a novel idea helping understand the pathogenesis of ADC.

  9. Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration

    Directory of Open Access Journals (Sweden)

    Brown Guy C

    2005-09-01

    Full Text Available Abstract Background Inflammation-activated glia are seen in many CNS pathologies and may kill neurons through the release of cytotoxic mediators, such as nitric oxide from inducible NO synthase (iNOS, and possibly superoxide from NADPH oxidase (NOX. We set out to determine the relative role of these species in inducing neuronal death, and to test the dual-key hypothesis that the production of both species simultaneously is required for significant neuronal death. Methods Primary co-cultures of cerebellar granule neurons and glia from rats were used to investigate the effect of NO (from iNOS, following lipopolysaccharide (LPS and/or cytokine addition or superoxide/hydrogen peroxide (from NOX, following phorbol 12-myristate 13-acetate (PMA, ATP analogue (BzATP, interleukin-1β (IL-1β or arachidonic acid (AA addition on neuronal survival. Results Induction of glial iNOS caused little neuronal death. Similarly, activation of NOX alone resulted in little or no neuronal death. However, if NOX was activated (by PMA or BzATP in the presence of iNOS (induced by LPS and interferon-γ then substantial delayed neuronal death occurred over 48 hours, which was prevented by inhibitors of iNOS (1400W, NOX (apocynin or a peroxynitrite decomposer (FeTPPS. Neurons and glia were also found to stain positive for nitrotyrosine (a putative marker of peroxynitrite only when both iNOS and NOX were simultaneously active. If NOX was activated by weak stimulators (IL-1β, AA or the fibrillogenic prion peptide PrP106-126 in the presence of iNOS, it caused microglial proliferation and delayed neurodegeneration over 6 days, which was prevented by iNOS or NOX inhibitors, a peroxynitrite decomposer or a NMDA-receptor antagonist (MK-801. Conclusion These results suggest a dual-key mechanism, whereby glial iNOS or microglial NOX activation alone is relatively benign, but if activated simultaneously are synergistic in killing neurons, through generating peroxynitrite. This

  10. Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

    OpenAIRE

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Salwa M. Abo El-khair; Helaly, Ahmed MN; Mahmoud, El-Hassanin M; Elshafey, Saad H

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl3) induced animal model of AD. Fifty adult rats included in this...

  11. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells

    OpenAIRE

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M.; Hill, Jim; Dua, Prerna; Lukiw, Walter J.

    2013-01-01

    Inducible micro RNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health and disease. Using miRNA arrays, RNA-sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot and bioinformatics analysis we have studied miRNA abundance and complexity in Alzheimer’s disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells we observe a c...

  12. Upregulation of p‑Akt by glial cell line‑derived neurotrophic factor ameliorates cell apoptosis in the hippocampus of rats with streptozotocin‑induced diabetic encephalopathy.

    Science.gov (United States)

    Cui, Weigang; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Yuan, Guoyan

    2016-01-01

    The loss of neurotrophic factor support has been shown to contribute to the development of the central nervous system. Glial cell line‑derived neurotrophic factor (GDNF), a potent neurotrophic factor, is closely associated with apoptosis and exerts neuroprotective effects on numerous populations of cells. However, the underlying mechanisms of these protective effects remain unknown. In the present study, a significant increase in Bax levels and DNA fragmentation was observed in the hippocampus obtained from the brains of diabetic rats 60 days after diabetes had been induced. The apoptotic changes were correlated with the loss of GDNF/Akt signaling. GDNF administration was found to reverse the diabetes‑induced Bax and DNA fragmentation changes. This was associated with an improvement in the level of p‑Akt/Akt. In addition, combination of GDNF with a specific inhibitor of the phosphoinositide 3‑kinase (PI3K)/Akt pathway, Wortmannin, significantly abrogated the effects of GDNF on the levels of p‑Akt/Akt, Bax and DNA fragmentation. However, a p38 mitogen‑activated proten kinase (MAPK) inhibitor, SB203580, had no effect on the expression of p‑Akt/Akt, Bax or DNA fragmentation. These results demonstrate the pivotal role of GDNF as well as the PI3K/Akt pathway, but not the MAPK pathway, in the prevention of diabetes‑induced neuronal apoptosis in the hippocampus. PMID:26549420

  13. Origin and development of neuropil glia of the Drosophila larval and adult brain: Two distinct glial populations derived from separate progenitors.

    Science.gov (United States)

    Omoto, Jaison Jiro; Yogi, Puja; Hartenstein, Volker

    2015-08-15

    Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular processes which associate with synapses and sheath-like processes which surround neuropil compartments, respectively. In this paper we characterize the development of NPG throughout fly brain development. We find that differentiated neuropil glia of the larval brain originate as a cluster of precursors derived from embryonic progenitors located in the basal brain. These precursors undergo a characteristic migration to spread over the neuropil surface while specifying/differentiating into primary ALG and EG. Embryonically-derived primary NPG are large cells which are few in number, and occupy relatively stereotyped positions around the larval neuropil surface. During metamorphosis, primary NPG undergo cell death. Neuropil glia of the adult (secondary NPG) are derived from type II lineages during the postembryonic phase of neurogliogenesis. These secondary NPG are much smaller in size but greater in number than primary NPG. Lineage tracing reveals that both NPG subtypes derive from intermediate neural progenitors of multipotent type II lineages. Taken together, this study reveals previously uncharacterized dynamics of NPG development and provides a framework for future studies utilizing Drosophila glia as a model. PMID:25779704

  14. The niche-derived glial cell line-derived neurotrophic factor (GDNF induces migration of mouse spermatogonial stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Lisa Dovere

    Full Text Available In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF, a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  15. Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior.

    Science.gov (United States)

    Arezoomandan, Reza; Haghparast, Abbas

    2016-03-01

    Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse. PMID:26745749

  16. Ablation of connexin30 in transgenic mice alters expression patterns of connexin26 and connexin32 in glial cells and leptomeninges.

    Science.gov (United States)

    Lynn, B D; Tress, O; May, D; Willecke, K; Nagy, J I

    2011-12-01

    Expression of connexin26 (Cx26), Cx30 and Cx43 in astrocytes and expression of Cx29, Cx32 and Cx47 in oligodendrocytes of adult rodent brain has been well documented, as has the interdependence of connexin expression patterns of macroglial cells in Cx32- and Cx47-knockout mice. To investigate this interdependence further, we examined immunofluorescence labelling of glial connexins in transgenic Cx30 null mice. Ablation of astrocytic Cx30, confirmed by the absence of immunolabelling for this connexin in all brain regions, resulted in the loss of its coupling partner Cx32 on the oligodendrocyte side of astrocyte-oligodendrocyte (A/O) gap junctions, but had no effect on the localization of astrocytic Cx43 and oligodendrocytic Cx47 at these junctions or on the distribution of Cx32 along myelinated fibres. Surprisingly, gene deletion of Cx30 led to the near total elimination of immunofluorescence labelling for Cx26 in all leptomeningeal tissues covering brain surfaces as well as in astrocytes of brain parenchyma. Moreover northern blot analysis revealed downregulation of Cx26 mRNA in Cx30-knockout brains. Our results support earlier observations on the interdependency of Cx30/Cx32 targeting to A/O gap junctions and further suggest that Cx26 mRNA expression is affected by Cx30 gene expression. In addition, Cx30 protein may be required for co-stabilization of gap junctions or for co-trafficking in cells. PMID:22098503

  17. Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yoon Hee [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Gupta, Mukesh Kumar, E-mail: goops@konkuk.ac.kr [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Oh, Shin Hye [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Uhm, Sang Jun [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Lee, Hoon Taek, E-mail: htl3675@konkuk.ac.kr [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of)

    2010-03-10

    This study evaluated the essentiality of glial cell line-derived neurotrophic factor (GDNF) for in vitro culture of established mouse multipotent adult germline stem (maGS) cell lines by culturing them in the presence of GDNF, leukemia inhibitory factor (LIF) or both. We show that, in the absence of LIF, GDNF slows the proliferation of maGS cells and result in smaller sized colonies without any change in distribution of cells to different cell-cycle stages, expression of pluripotency genes and in vitro differentiation potential. Furthermore, in the absence of LIF, GDNF increased the expression of male germ-line genes and repopulated the empty seminiferous tubule of W/W{sup v} mutant mouse without the formation of teratoma. GDNF also altered the genomic imprinting of Igf2, Peg1, and H19 genes but had no effect on DNA methylation of Oct4, Nanog and Stra8 genes. However, these effects of GDNF were masked in the presence of LIF. GDNF also did not interfere with the multipotency of maGS cells if they are cultured in the presence of LIF. In conclusion, our results suggest that, in the absence of LIF, GDNF alters the growth characteristics of maGS cells and partially impart them some of the germline stem (GS) cell-like characteristics.

  18. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID:26564715

  19. Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

    Science.gov (United States)

    Morale, M C; Gallo, F; Tirolo, C; Testa, N; Caniglia, S; Marletta, N; Spina-Purrello, V; Avola, R; Caucci, F; Tomasi, P; Delitala, G; Barden, N; Marchetti, B

    2001-08-01

    Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface. PMID:11488988

  20. Combination effects of epidermal growth factor and glial cell line-derived neurotrophic factor on the in vitro developmental potential of porcine oocytes.

    Science.gov (United States)

    Valleh, Mehdi Vafaye; Rasmussen, Mikkel Aabech; Hyttel, Poul

    2016-06-01

    The developmental potential of in vitro matured porcine oocytes is still lower than that of oocytes matured and fertilized in vivo. Major problems that account for the lower efficiency of in vitro production include the improper nuclear and cytoplasmic maturation of oocytes. With the aim of improving this issue, the single and combined effects of epidermal growth factor (EGF) and glial cell line-derived neurotrophic factor (GDNF) on oocyte developmental competence were investigated. Porcine cumulus-oocyte cell complexes (COCs) were matured in serum-free medium supplemented with EGF (0, 10 or 50 ng/ml) and/or GDNF (0, 10 or 50 ng/ml) for 44 h, and subsequently subjected to fertilization and cultured for 7 days in vitro. The in vitro-formed blastocysts derived from selected growth factor groups (i.e. EGF = 50 ng/ml; GDNF = 50 ng/ml; EGF = 50 ng/ml + GDNF = 50 ng/ml) were also used for mRNA expression analysis, or were subjected to Hoechst staining. The results showed that the addition of EGF and/or GDNF during oocyte maturation dose dependently enhanced oocyte developmental competence. Compared with the embryos obtained from control or single growth factor-treated oocytes, treatment with the combination of EGF and GDNF was shown to significantly improve oocyte competence in terms of blastocyst formation, blastocyst cell number and blastocyst hatching rate (P competency and blastocyst quality. PMID:26350562

  1. Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats

    Directory of Open Access Journals (Sweden)

    Wenzhan Tu

    2015-01-01

    Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

  2. Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

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    Sergio Comincini

    2009-01-01

    Full Text Available In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

  3. Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells

    International Nuclear Information System (INIS)

    This study evaluated the essentiality of glial cell line-derived neurotrophic factor (GDNF) for in vitro culture of established mouse multipotent adult germline stem (maGS) cell lines by culturing them in the presence of GDNF, leukemia inhibitory factor (LIF) or both. We show that, in the absence of LIF, GDNF slows the proliferation of maGS cells and result in smaller sized colonies without any change in distribution of cells to different cell-cycle stages, expression of pluripotency genes and in vitro differentiation potential. Furthermore, in the absence of LIF, GDNF increased the expression of male germ-line genes and repopulated the empty seminiferous tubule of W/Wv mutant mouse without the formation of teratoma. GDNF also altered the genomic imprinting of Igf2, Peg1, and H19 genes but had no effect on DNA methylation of Oct4, Nanog and Stra8 genes. However, these effects of GDNF were masked in the presence of LIF. GDNF also did not interfere with the multipotency of maGS cells if they are cultured in the presence of LIF. In conclusion, our results suggest that, in the absence of LIF, GDNF alters the growth characteristics of maGS cells and partially impart them some of the germline stem (GS) cell-like characteristics.

  4. Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct

    Directory of Open Access Journals (Sweden)

    X. Joann You

    2011-01-01

    Full Text Available Work has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonrodent animal model of this therapeutic strategy, we previously derived NPCs from the fetal cat brain (cNPCs. Here we use bicistronic feline lentiviral vectors to transduce cNPCs with glial cell-derived neurotrophic factor (GDNF together with a GFP reporter gene. Transduction efficacy is assessed, together with transgene expression level and stability during induction of cellular differentiation, together with the influence of GDNF transduction on growth and gene expression profile. We show that GDNF overexpressing cNPCs expand in vitro, coexpress GFP, and secrete high levels of GDNF protein—before and after differentiation—all qualities advantageous for use as a cell-based approach in feline models of neural degenerative disease.

  5. Low-level bisphenol A increases production of glial fibrillary acidic protein in differentiating astrocyte progenitor cells through excessive STAT3 and Smad1 activation

    International Nuclear Information System (INIS)

    The effects of bisphenol A (BPA) on the differentiation of serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, were examined. SFME cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10 ng/ml bone morphogenetic protein 2 (BMP2) to increase glial fibrillary acidic protein (GFAP) expression and induce cell differentiation. Various concentrations of BPA (0.1 pg/ml-1 μg/ml) were then added to determine their effects on the cell differentiation. SFME cells were effectively differentiated by LIF and BMP2 in completely serum-free cultures. Cell proliferation following cell differentiation was not significantly affected by low-level BPA. However, GFAP expression was significantly increased in SFME cells in the presence of 1-100 pg/ml BPA. These increases were due to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA

  6. Role of T cell – glial cell interactions in creating and amplifying Central Nervous System inflammation and Multiple Sclerosis disease symptoms

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    Eric S. Huseby

    2015-08-01

    Full Text Available Multiple Sclerosis (MS is an inflammatory disease of the Central Nervous System (CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought of as a T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified gray matter lesions in MS patients, suggesting that CNS antigens other than myelin proteins may be involved during the MS disease process. We have recently found that T cells targeting astrocyte-specific antigens can drive unique aspects of inflammatory CNS autoimmunity, including the targeting of gray matter and white matter of the brain and inducing heterogeneous clinical disease courses. In addition to being a target of T cells, astrocytes play a critical role in propagating the inflammatory response within the CNS through cytokine induced NF-ΚB signaling. Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell – glial cell interactions and its contributions to CNS autoimmunity.

  7. Astrócitos imunorreativos à proteína glial fibrilar ácida (GFAP) em sistema nervoso central de equinos normais e de equinos com leucoencefalomalácia Glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in the Central Nervous System of normal horses and horses with leukoencephalomalacia

    OpenAIRE

    Karen Regina Lemos; Antonio Carlos Alessi

    1999-01-01

    A proteína glial fibrilar ácida (GFAP), subunidade dos filamentos intermediários do citoesqueleto celular, está presente no citoplasma de astrócitos. Técnicas imunohistoquímicas com anticorpos primários anti-GFAP são geralmente empregadas para identificar astrócitos no sistema nervoso, permitindo verificar também sua hipertrofia. Vários estudos mostram a distribuição, a morfologia e a citoarquitetura de astrócitos em várias regiões do SNC do homem e de animais de laboratório. No entanto, em a...

  8. Age features in protein’s composition modifications of the neurospecifical and glial intermediate filaments in different parts of the red’s brain depend on ionization radiation actions

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    Romanenko L.A.

    2008-01-01

    Full Text Available In this work we compare the main changes in protein composition of intermediate filaments due to ionization radiation actions on old and yang rats. The objects of our investigation were 120 rats (60 old and 60 yangs. They were divided on groups in depend on ionization radiation action duration – 1 day, 1,2 and 3 week, and the control group. The action of ionization radiation was modeled with the help of “РУМ-17” in the fate 0,00129 Kl/kg. Brains were divided on parts (cortex, cerebellum, gypocamp, homogenized, centrifugised. The quantity of glial and neuronal filaments (NF was defined by the rocket-lineal immunoelectrophoresis; immunoblotting with specific antibodies was used for qualitative changes defining. After ionization radiation action we observed no age features in protein composition of intermediate filaments. All changes were due to duration of the ionization radiation action. Main changes in neurofilaments were associated with decrease of 210 kDa subunit. Products of degradation (40 - 48 kDa of fibrillar glial filaments were observed on the 2 week of experiment. There were biphasic changes in glial fibrillar acidic protein in cerebellum and gypocamp of yang and old rats.

  9. Effects of intrathecal injection of glial cell inhibitor on spinal cord astrocytes following chronic compression of dorsal root ganglia in rats

    Institute of Scientific and Technical Information of China (English)

    Xianhong Zhang; Wen Shen; Mingde Wang; Yinming Zeng

    2009-01-01

    BACKGROUND: Astrocytes are considered to provide nutritional support in the central nervous system. However, recent studies have confirmed that astrocytes also play an important role in chronic pain. OBJECTIVE: To investigate the effects of intrathecal injection of fluorocitrate, minocycline or both on astrocyte activation and proliferation in the spinal dorsal horn of compressed dorsal root ganglion in rats. DESIGN, TIME AND SETTING: The neurology randomized controlled animal study was performed at the Jiangsu Institute of Anesthesia Medicine, from September 2006 to April 2007. MATERIALS: A total of 96 male Sprague Dawley rats, aged 6-8 weeks, were selected for this study. Following intrathecal catheterization, 80 rats underwent steel bar insertion into the L4-5 intervertebral foramina to make a stable compression on the L4-5 posterior root ganglion. Thus rat models of ganglion compression were established. Minocycline and fluorocitrate were purchased from Sigma, USA. METHODS: A total of 96 rats were randomly and equally divided into six groups. Rat L4, L5 transverse process and intervertebral foramina were exposed in the sham operation group, but without steel bar insertion. The model group did not receive any manipulations. Rats in the phosphate buffered saline (PBS) group were intrathecally injected with 0.01 mmol/L PBS (20 μL). Rats in the fluorocitrate group were subjected to 1 μmol/L fluorocitrate (20 μL). Rats in the minocycline group were intrathecally injected with 5 g/L minocycline (20 μL). Rats in the minocycline and fluorocitrate group received a mixture (20 μL) of 5 g/L minocycline and 1 μmol/L fluorocitrate. Following model establishment, drugs were administered once a day. MAIN OUTCOME MEASURES: At 7 and 14 days following model induction, glial fibrillary acidic protein expression in the spinal dorsal horn was measured by immunofluorescence microscopy. Six sections with significant glial fibrillary acidic protein -positive expression were

  10. Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

    Science.gov (United States)

    Galindo, Cristi L.; Kasasbeh, Ehab; Murphy, Abigail; Ryzhov, Sergey; Lenihan, Sean; Ahmad, Farhaan A.; Williams, Philip; Nunnally, Amy; Adcock, Jamie; Song, Yanna; Harrell, Frank E.; Tran, Truc‐Linh; Parry, Tom J.; Iaci, Jen; Ganguly, Anindita; Feoktistov, Igor; Stephenson, Matthew K.; Caggiano, Anthony O.; Sawyer, Douglas B.; Cleator, John H.

    2014-01-01

    Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart. PMID:25341890

  11. Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated Glial-derived neurotrophic factor combined with early rehabilitation training

    Institute of Scientific and Technical Information of China (English)

    Han Qingquan; Xiang Jingjing; Zhang Yun; Qiao Hujun; Shen Yongwei; Zhang Chun

    2014-01-01

    Background Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims.The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats.Then besides the sham operation group,the SCI rats were randomly divided into four groups:natural healing group,gene therapy group,rehabilitation training group,and combination therapy group (gene therapy in combination with rehabilitation training).Motor dysfunction,protein expression of GDNF,edema formation,and cell injury were examined 7,14,and 21 days after trauma.Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF,especially after the 14th day,and could protect the motor neuron ceils.Early rehabilitative treatment resulted in significantly improved motor function,reduced edema formation,and protected the cells from injury,especially after the 7th and 14th days,and increased the GDNF expression in the damaged area,which was most evident after Day 14.The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

  12. Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction.

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    Mattias Vågberg

    Full Text Available Neurofilament light (NFL and Glial Fibrillary Acidic Protein (GFAP are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF using magnetic resonance imaging (MRI. Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated.To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF.The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis and 48 of the volunteers underwent determination of BPF using MRI.Mean (±SD NFL was 355 ng/L (±214, mean GFAP was 421 ng/L (±129 and mean BPF was 0.867 (±0.035. All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance.This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age.

  13. Modulation of the tyrosine kinase receptor Ret/glial cell-derived neurotrophic factor (GDNF) signaling: a new player in reproduction induced anterior pituitary plasticity?

    Science.gov (United States)

    Guillou, Anne; Romanò, Nicola; Bonnefont, Xavier; Le Tissier, Paul; Mollard, Patrice; Martin, Agnès O

    2011-02-01

    During gestation, parturition, and lactation, the endocrine axis of the dam must continually adapt to ensure the continual and healthy development of offspring. The anterior pituitary gland, which serves as the endocrine interface between the brain and periphery, undergoes adaptations that contribute to regulation of the reproductive axis. Growth factors and their receptors are potential candidates for intrapituitary and paracrine factors to participate in the functional and anatomical plasticity of the gland. We examined the involvement of the growth factor glial cell-derived neurotrophic factor (GDNF) and its receptor tyrosine kinase rearranged during transfection (Ret) in the physiological functional and anatomical plasticity of the anterior pituitary gland. We found that variations in both expression and subcellular localization of Ret during gestation and lactation are temporally correlated with changes in pituitary gland function. We showed that Ret/GDNF signaling could endorse two different functional roles depending on the physiological status. At the end of lactation and after weaning, Ret was colocalized with markers of apoptosis. We found that Ret could therefore act as a physiological dependence receptor capable of inducing apoptosis in the absence of GDNF. In addition, we identified the follicullostellate cell as a probable source for intrapituitary GDNF and proposed GDNF as a potential physiological modulator of endocrine cell function. During all stages studied, we showed that acute application of GDNF to pituitary slices was able to modulate both positively and negatively intracellular calcium activity. Altogether our results implicate Ret/GDNF as a potent pleiotropic factor able to influence pituitary physiology during a period of high plasticity. PMID:21239429

  14. Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction

    Directory of Open Access Journals (Sweden)

    Zhang LY

    2015-03-01

    Full Text Available Li-Yong Zhang,1,* Tao Xing,1,* Li-Xin Du,1,* Qing-Min Li,2 Wei-Dong Liu,1 Ji-Yue Wang,1 Jing Cai31Department of neurosurgery, Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of China; 2Department of Neurosurgery, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Department of Neurosurgery, LinYi People Hospital, LinYi, Shandong, People’s Republic of China*These authors contributed equally to this workBackground: Glial cell line-derived neurotrophic factor (GDNF is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF.Methods: A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes.Results: This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF.Conclusion: This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice.Keywords: lateral flow biosensor, molecular translator, isothermal strand-displacement polymerization reaction

  15. Effect of basic fibroblast growth factor on the expression of glial fibrillary acidic protein after tractive spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; L(U) Bo; TU Chong-qi; CHI Lei-ting; WANG Guang-lin; PEI Fu-xing

    2005-01-01

    Objective: To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spinal cord function.Methods: The rats were subjected to tractive spinal cord injury at T13-L2. Cortical somatosensory-evoked potential (CSEP) was closely monitored and when P1-N1 wave amplitude decreased to 70% of that before operation, a small-bore catheter was inserted below the injured plane through subarachnoid cavity. In the treatment groups, 20 μl of bFGF solution (containing 20 μg of bFGF) was injected through the catheter right after the operation and 1,2, 3, 4, 8, 12 and 24 h postoperatively. In the control group, same volume of normal saline was injected and every four rats were killed at 1, 4, 7, 14 and 21 d after the operation. Combined behavior score (CBS) and electro-physiological examination were adopted to evaluate function recovery. Expression of GFAP was observed by immuno-histochemical staining and was analyzed quantitatively by computer image analysis.Results: There was statistically significant difference in GFAP-positive cells between bFGF treatment group and the control group (P<0.01). Similar tendency was indicated by the results of CBS and CSEP.Conclusions: bFGF can induce large expression of GFAP after tractive spinal cord injury in rats and promote spinal function recovery, which is highly important for spinal cord regeneration.

  16. Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats

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    Nakagawa Takayuki

    2008-12-01

    Full Text Available Abstract Background The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats. Results Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation. Conclusion These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.

  17. NG2细胞与中枢神经系统疾病%Roles of NG2 glial cells in diseases of the central nervous system

    Institute of Scientific and Technical Information of China (English)

    许建平; 赵杰; 李韶

    2011-01-01

    NG2 cells are a novel distinct class of central nervous system(CNS)glial cells,characterized by the expression of the chondroitin sulfate proteoglycan NG2.They have been detected in a variety of human CNS diseases.As morphological,physiological and biomolecular studies of NG2 cells have been conducted,their roles have been gradually revealed.Research on cellular and molecular mechanisms in the pathophysiological state was built on the preliminary findings of their physiological functions; and in turn,this helps to clarify their physiological roles and leads to the identification of novel therapeutic targets.This review summarizes recent findings regarding the potential roles of NG2 cells in traumatic brain injury,multiple sclerosis,glioma,epilepsy,Alzheimer's disease and electroconvulsive therapy for depression.%NG2细胞是新发现的一类广泛存在于成熟和发育期中枢神经系统的胶质细胞群体.这些细胞表面表达NG2硫酸软骨素蛋白多糖,因而常被称作NG2细胞.随着NG2细胞形态学研究的深入,NG2胶质细胞的功能也越来越受到关注.NG2细胞在人类多种中枢神经系统疾病中扮演重要角色.本文结合最新的研究报道,就其在一些常见的中枢神经系统疾病中的作用进行概括综述.

  18. Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Davies Jeannette E

    2008-09-01

    Full Text Available Abstract Background Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes. Results We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs treated with bone morphogenetic protein-4 (BMP-4 can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAsCNTF, the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDACNTF cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAsBMP did not exhibit pain syndromes. Conclusion Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair.

  19. Deconstructing the Iboga Alkaloid Skeleton: Potentiation of FGF2-induced Glial Cell Line-Derived Neurotrophic Factor Release by a Novel Compound.

    Science.gov (United States)

    Gassaway, Madalee M; Jacques, Teresa L; Kruegel, Andrew C; Karpowicz, Richard J; Li, Xiaoguang; Li, Shu; Myer, Yves; Sames, Dalibor

    2016-01-15

    Modulation of growth factor signaling pathways in the brain represents a new experimental approach to treating neuropsychiatric disorders such as depression, anxiety, and addiction. Neurotrophins and growth factors exert synaptic, neuronal, and circuit level effects on a wide temporal range, which suggests a possibility of rapid and lasting therapeutic effects. Consequently, identification of small molecules that can either enhance the release of growth factors or potentiate their respective pathways will provide a drug-like alternative to direct neurotrophin administration or viral gene delivery and thus represents an important frontier in chemical biology and drug design. Glial cell line-derived neurotrophic factor (GDNF), in particular, has been implicated in marked reduction of alcohol consumption in rodent addiction models, and the natural product ibogaine, a substance used traditionally in ritualistic ceremonies, has been suggested to increase the synthesis and release of GDNF in the dopaminergic system in rats. In this report, we describe a novel iboga analog, XL-008, created by unraveling the medium size ring of the ibogamine skeleton, and its ability to induce release of GDNF in C6 glioma cells. Additionally, XL-008 potentiates the release of GDNF induced by fibroblast growth factor 2 (FGF2), another neurotrophin implicated in major depressive disorder, increasing potency more than 2-fold (from 7.85 ± 2.59 ng/mL to 3.31 ± 0.98 ng/mL) and efficacy more than 3-fold. The GDNF release by both XL-008 and the FGF2/XL-008 mixture was found to be mediated through the MEK and PI3K signaling pathways but not through PLCγ in C6 glioma cells. PMID:26517751

  20. Progressive retinal degeneration and glial activation in the CLN6 (nclf mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.

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    Myriam Mirza

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6 (nclf mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6 (nclf retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6 (nclf retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA, could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6 (nclf mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6 (nclf retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6 (nclf retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds.

  1. Intravenous glial growth factor 2 (GGF2 isoform of neuregulin-1β improves left ventricular function, gene and protein expression in rats after myocardial infarction.

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    Michael F Hill

    Full Text Available AIMS: Recombinant Neuregulin (NRG-1β has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF. A number of factors may influence the effect of NRG-1β on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1β isoform, glial growth factor 2 (GGF2, in rats with myocardial infarction (MI and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis. METHODS AND RESULTS: Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production. CONCLUSIONS: This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.

  2. Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish Population.

    Science.gov (United States)

    Orenay-Boyacioglu, Seda; Coskunoglu, Aysun; Caki, Zerrin; Cam, Fethi Sirri

    2016-08-01

    Glial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction-based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression pattern of GDNF. PMID:27180191

  3. Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells

    Institute of Scientific and Technical Information of China (English)

    Hong-jun WANG; Jun-ping CAO; Jing-kao YU; Dian-shuai GAO

    2007-01-01

    Aim: To explore the intracellular mechanisms underlying the survival/differentia-don effect of the glial cell line-derived neurotrophic factor (GDNF) on dopamine(DA) cells. Methods: Midbrain slice culture and primary cell culture were established, and the cultures were divided into 3 groups: control group, GDNF group, and the phosphatidylinositol 3-kinase/Akt (PI3-K/Akt) pathway-inhibited group. Then the expression of tyrosine hydroxylase (TH) was detected by immunostaining as well as Western blotting. Results: GDNF treatment induced an increase in the number of TH-immunoreactive (ir) cells and the neurite number of TH-ir cells, as well as in the level of TH expression in cultures (Number of TH-ir cells in the slice culture: control group, 8.76±0.75; GDNF group, 18.63±0.95.Number of TH-ir cells and neurite number of TH-ir cells in cell culture: controlgroup, 3.65±0.88 and 2.49±0.42; GDNF group, 6.01±0.43 and 4.89±0.46). Meanwhile, the stimulation of cultured cells with GDNF increased the phosphorylation of Akt, which is a downstream effector of PI3-K/Akt. The effects of GDNF were specifically blocked by the inhibitor of the PI3-K/Akt pathway, wortmannin (Number of TH-ir cells in slice culture: PI3-K/Akt pathway-inhibited group, 6.98±0.58. Num-ber of TH-ir cells and neurite number of TH-ir cells in cell culture: PI3-K/Aktpathway-inhibited group, 3.79±0.62 and 2.50±0.25, respectively). Conclusion: The PI3-K/Akt pathway mediates the survival/differentiation effect of GDNF on DA cells.8±0.58.

  4. Semicontinuous Low-Dose-Rate Teletherapy for the Treatment of Recurrent Glial Brain Tumors: Final Report of a Phase I/II Study

    International Nuclear Information System (INIS)

    Purpose: Semicontinuous low-dose-rate teletherapy (SLDR) is a novel irradiation strategy that exploits the increased radiosensitivity of glial cells in a narrow range of reduced dose rate. We present the final report of a prospective Phase I/II study testing the feasibility of SLDR for the treatment of recurrent gliomas. Methods and Materials: Patients with previously irradiated recurrent gliomas were enrolled from November 1993 to March 1998. Patients received SLDR, delivered 6 to 8 hours/day at a dose rate of 40 to 50 cGy/hour for a total dose of 30 to 35 Gy given over 12 days using a modified cobalt-60 treatment unit. Acute central nervous system toxicity after SLDR treatment was the primary endpoint. Overall survival was a secondary endpoint. Results: Twenty patients were enrolled (14 World Health Organization Grade 4 glioma, 5 Grade 2 glioma, 1 ependymoma). No patients developed ≥Grade 3 central nervous system toxicity at 3 months without radiographic evidence of tumor progression. Overall survival after SLDR was 56% at 6 months, 28% at 12 months, and 17% at 24 months. One patient survived >48 months, and 1 patient survived >60 months after SLDR treatment. Re-resection before SLDR treatment significantly improved 1-year overall survival for all patients and patients with Grade 4 glioma. Conclusion: The delivery of SLDR is feasible in patients with recurrent gliomas and resulted in improved outcomes for patients who underwent re-resection. There were 2 long-term survivors (>48 months). This pilot study supports the notion that reduced dose rate influences the efficacy and tolerance of reirradiation in the treatment of recurrent gliomas.

  5. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease.

    Science.gov (United States)

    Ojha, Shreesh; Javed, Hayate; Azimullah, Sheikh; Haque, M Emdadul

    2016-07-01

    Parkinson disease (PD) is a neurodegenerative disease characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta (SNc) area. The present study was undertaken to evaluate the neuroprotective effect of β-caryophyllene (BCP) against rotenone-induced oxidative stress and neuroinflammation in a rat model of PD. In the present study, BCP was administered once daily for 4 weeks at a dose of 50 mg/kg body weight prior to a rotenone (2.5 mg/kg body weight) challenge to mimic the progressive neurodegenerative nature of PD. Rotenone administration results in oxidative stress as evidenced by decreased activities of superoxide dismutase, catalase, and depletion of glutathione with a concomitant rise in lipid peroxidation product, malondialdehyde. Rotenone also significantly increased pro-inflammatory cytokines in the midbrain region and elevated the inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Further, immunohistochemical analysis revealed loss of dopaminergic neurons in the SNc area and enhanced expression of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), indicators of microglia activation, and astrocyte hypertrophy, respectively, as an index of inflammation. However, treatment with BCP rescued dopaminergic neurons and decreased microglia and astrocyte activation evidenced by reduced Iba-1 and GFAP expression. BCP in addition to attenuation of pro-inflammatory cytokines and inflammatory mediators such as COX-2 and iNOS, also restored antioxidant enzymes and inhibited lipid peroxidation as well as glutathione depletion. The findings demonstrate that BCP provides neuroprotection against rotenone-induced PD and the neuroprotective effects can be ascribed to its potent antioxidant and anti-inflammatory activities. PMID:27316720

  6. Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to ‘composite’ blast.

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    VictorPrima

    2012-02-01

    Full Text Available A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position towards blast generated by an external shock tube. In this study, we further characterized blast producing moderate TBI and defined ‘composite’ blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast, but negligible skull movement upon peak overpressure exposure off-axis (primary blast. Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, sICAM, and L-selectin along with neurotrophic factor NGF-beta were increased in serum within 6 hours post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2 were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast setups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with

  7. Redução da expressão astrocitária de proteína glial fibrilar ácida em cães tratados com dexametasona Decrease in the astrocytic expression of glial fibrillary acidic protein in dogs treated with dexamethasone

    Directory of Open Access Journals (Sweden)

    Eduardo Fernandes Bondan

    2013-03-01

    Full Text Available A proteína glial fibrilar ácida (GFAP constitui o principal marcador dos astrócitos, as células gliais mais numerosas do tecido nervoso e que exibem receptores a diversos hormônios esteroidais, os quais exercem aparente influência sobre a expressão gênica das mesmas. O objetivo do presente estudo foi o de avaliar se a administração de dexametasona (DX em protocolos terapêuticos para cães seria capaz de afetar a expressão astrocitária dessa proteína. Para tal, amostras da ponte e da medula espinhal torácica de cães, tratados (n=6 ou não (n=6 com DX, foram submetidas à marcação imuno-histoquímica para a GFAP e a reatividade astrocitária foi determinada por colorimetria em um sistema computacional de análise de imagens. Diferença estatisticamente significativa foi constatada para as médias das áreas marcadas para GFAP na ponte de cães tratados e não-tratados com DX, assim como na medula espinhal torácica dos que haviam recebido previamente o corticoide ou não, com clara tendência, induzida pela droga, de redução da expressão astrocitária da proteína. Além disso, a expressão de GFAP na medula espinhal foi maior que na ponte, independentemente do emprego de DX ou não.Glial fibrillary acidic protein (GFAP is the most important marker of astrocytes, that are the major glial cells in the nervous tissue and exhibit receptors to several steroid hormones, which have an apparent influence in their genic expression. The aim of this study was to evaluate if dexamethasone (DX administration in therapeutic protocols to dogs would be capable of affecting the astrocytic expression of the protein. Samples from the pons and the spinal cord of dogs, treated (n=6 or not (n=6 with DX, were submitted to GFAP immunohistochemical staining and astrocytic reactivity was determined by colorimetry in a computer system for image analysis. Difference statistically significant was noted for the mean areas stained with GFAP in the pons of

  8. Differential effect of maternal diet supplementation with α-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains

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    Cruz-Hernandez Cristina

    2010-01-01

    Full Text Available Abstract Background Dietary long-chain polyunsaturated fatty acids (LC-PUFA are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE and phosphatidylserine (PS in the neonates. Methods Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55% and eicosapentaenoic acid (EPA, 0.75% of total fatty acids or α-linolenic acid (ALA, 2.90%. At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA profile. Data were analyzed by bivariate and multivariate statistics. Results In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P Conclusion The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.

  9. Protective effect of liposome-mediated glial cell line-derived neurotrophic factor gene transfer in vivo on motoneurons following spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    鲁凯伍; 陈哲宇; 侯铁胜

    2004-01-01

    Objective:To investigate the effect of liposomemediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats.Methods: Sixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RTPCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale.Results: RT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group (20.4±3.2, 21.7±3.6, 22.5±3.4) was more than that in control group ( 16.8±2.8, 17.3 ± 2.7,18.2±3.2, P<0.05). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group (74.2± 25.8, 98.7± 31.6 was less than that in control group (98.5 ±32.2, 134.6 ±45.2, P<0.01), and the mean gray of ACP in GDNF group (84.5±32.6, 79.5±28.4) was more than that in control group (61.2±24.9,52.6±19.9, P<0.01). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<0.05).Conclusions: GDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incompleted spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating

  10. P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons

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    Chen Yong

    2012-02-01

    Full Text Available Abstract Background The purinergic P2X3 receptor (P2X3R expressed in the dorsal root ganglion (DRG sensory neuron and the P2X7 receptor (P2X7R expressed in the surrounding satellite glial cell (SGC are two major receptors participating in neuron-SGC communication in adult DRGs. Activation of P2X7Rs was found to tonically reduce the expression of P2X3Rs in DRGs, thus inhibiting the abnormal pain behaviors in adult rats. P2X receptors are also actively involved in sensory signaling in developing rodents. However, very little is known about the developmental change of P2X7Rs in DRGs and the interaction between P2X7Rs and P2X3Rs in those animals. We therefore examined the expression of P2X3Rs and P2X7Rs in postnatal rats and determined if P2X7R-P2X3R control exists in developing rats. Findings We immunostained DRGs of immature rats and found that P2X3Rs were expressed only in neurons and P2X7Rs were expressed only in SGCs. Western blot analyses indicated that P2X3R expression decreased while P2X7R expression increased with the age of rats. Electrophysiological studies showed that the number of DRG neurons responding to the stimulation of the P2XR agonist, α,β-meATP, was higher and the amplitudes of α,β-meATP-induced depolarizations were larger in immature DRG neurons. As a result, P2X3R-mediated flinching responses were much more pronounced in immature rats than those found in adult rats. When we reduced P2X7R expression with P2X7R-siRNA in postnatal and adult rats, P2X3R-mediated flinch responses were greatly enhanced in both rat populations. Conclusions These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants.

  11. Activation of the Wnt/β-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    International Nuclear Information System (INIS)

    Highlights: ► Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. ► β-catenin translocated from the cell membrane to the nucleus in the ALS mice. ► Wnt3a, β-catenin and Cyclin D1 co-localized for astrocytes were all increased. ► BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. ► BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, β-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/β-catenin signaling pathway. We determined the expression of Wnt3a, β-catenin, and Cyclin D1 in the adult spinal cord of SOD1G93A ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, β-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, β-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, β-catenin or Cyclin D1 in mature GFAP+ astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/β-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This

  12. Time-dependent changes of glial fibriliary acidic protein and cytosolic phospholipase A2 in hippocampal area of focal cerebral ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Qingzhou Cheng; Xingui Ming

    2006-01-01

    BACKGROUND: Interaction between astrocyte and neuron may two-dimensionally influence on ischemic injury; however, glial fibriliary acidic protein (GFAP) and cytosolic phospholipase A2 (cPLA2) are both important markers to reflect changes of astrocyte and neuron after cerebral ischemia, respectively.OBJECTIVE: To observe the changes of GFAP and positive cPLA2 cells in hippocampal area of model rats with focal cerebral ischemia in various phases of cerebral ischemia/reperfusion.DESIGN: Randomized contrast observation.SETTTNG: Department of Basic Medical Science, Medical College of Wuhan Polytechnic University; Faculty of Human Anatomy and Histology & Embryology, Medical College of Wuhan University.MATERIALS: The experiment was carried out in the Department of Basic Medical Science, Medical College of Wuhan Industry College from May to June 2004. A total of 28 healthy SD rats of either gender and weighing 200-250 g were provided by Animal Department of Medical College of Jianghan University.METHODS: All 28 rats were randomly divided into 7 groups, including sham operation group, 2-, 6-, 12-,24- and 48-reperfusion groups, and triphenyltetrazolium chloride (TTC) group, with 4 in each group. Two hours after ischemia, ischemia/reperfusion models were established in left middle cerebral artery (MCA);common carotid artery was ligated and line cork was inserted into it with the depth of (1.8±0.5) cm. Rats in sham operation group were inserted with the depth of 1.0 cm, and other operations were as the same as those in 2-hour ischemia/reperfusion groups. Models in TTC group were established as the same as those in 2-hour ischemia/24-hour reperfusion group, and they were used to evaluate the therapeutic effect.Changes of GFAP and cPLA2 in hippocampal area in various phases were detected with immunohistochemical method.MATN OUTCOME MEASURES: Changes of GFAP and positive cPLA2 cells in hippocampal area of rats with focai cerebral ischemia in various phases of ischemia

  13. Changes in skin levels of two neutotrophins (glial cell line derived neurotrohic factor and neurotrophin-3) cause alterations in cutaneous neuron responses to mechanical stimuli

    Institute of Scientific and Technical Information of China (English)

    Jeffrey Lawson; Sabrina L. Mcllwrath; H. Richard Koerber

    2008-01-01

    Neurotrophins are important for the development and maintenance of both high and low threshold mechanoreceptors (HTMRs and LTMRs). In this series of studies, the effects of constitutive overexpression of two different neurotrophins, neurotrophin-3 (NT-3) and glial cell line derived neurotrohic factor (GDNF), were examined. Previous studies indicated that both of them may be implicated in the normal development of mouse dorsal root ganglion (DRG) neurons. Neurons from mice transgenically altered to overexpress NT-3 or GDNF (NT-3-OE or GDNF-OE mice) in the skin were examined using several physiological, immunohistochemi-cal and molecular techniques. Ex vivo skin/nerve/DRG/spinal cord and skin/nerve preparations were used to determine the response characteristics of the cutaneous neurons; immunohistochemistry was used to examine the biochemical phenotype of DRG cells and the skin; RT-PCR was used to examine the levels of candidate ion channels in skin and DRG that may correlate with changes in physiologi-cal responses. In GDNF-OE mice, I-isolectin B4 (IB4)-immunopositive C-HTMRs (nociceptors), a large percentage of which are sensitive to GDNF, had significantly lower mechanical thresholds than wildtype (WT) neurons. Heat thresholds for the same cells were not different. Mechanical sensitivity changes in GDNF-OE mice were correlated with significant increases in acid sensing ion channels 2a (ASIC2a) and 2b (ASIC2b) and transient receptor potential channel AI (TRPAI), all of which are putative mechanosensitive ion channels. Overexpression of NT-3 affected the responses of A-LTMRs and A-HTMRs, hut had no effect on C-HTMRs. Slowly adapting type 1 (SA1) LTMRs and A-HTMRs had increased mechanical sensitivity compared to WT. Mechanical sensitivity was correlated with significant increases in acid-sensing ion channels ASIC1 and ASIC3. This data indicates that both neurotrophins play roles in determining mechanical thresholds of cutaneous HTMRs and LTMRs and that sensitivity

  14. Activation of the Wnt/{beta}-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yanchun [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Guan, Yingjun, E-mail: guanyj@wfmc.edu.cn [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Liu, Huancai [Department of Orthopedic, Affiliated Hospital, Weifang Medical University, Weifang, Shandong (China); Wu, Xin; Yu, Li; Wang, Shanshan; Zhao, Chunyan; Du, Hongmei [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Wang, Xin, E-mail: xwang@rics.bwh.harvard.edu [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

    2012-04-06

    neurodegeneration activates the Wnt/{beta}-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This mechanism may be significant in clinical gene therapy.

  15. Perineuronal satellite neuroglia in the telencephalon of New Caledonian crows and other Passeriformes: evidence of satellite glial cells in the central nervous system of healthy birds?

    Directory of Open Access Journals (Sweden)

    Felipe S. Medina

    2013-07-01

    Full Text Available Glia have been implicated in a variety of functions in the central nervous system, including the control of the neuronal extracellular space, synaptic plasticity and transmission, development and adult neurogenesis. Perineuronal glia forming groups around neurons are associated with both normal and pathological nervous tissue. Recent studies have linked reduction in the number of perineuronal oligodendrocytes in the prefrontal cortex with human schizophrenia and other psychiatric disorders. Therefore, perineuronal glia may play a decisive role in homeostasis and normal activity of the human nervous system. Here we report on the discovery of novel cell clusters in the telencephala of five healthy Passeriforme, one Psittaciform and one Charadriiforme bird species, which we refer to as Perineuronal Glial Clusters (PGCs. The aim of this study is to describe the structure and distribution of the PGCs in a number of avian species. PGCs were identified with the use of standard histological procedures. Heterochromatin masses visible inside the nuclei of these satellite glia suggest that they may correspond to oligodendrocytes. PGCs were found in the brains of nine New Caledonian crows, two Japanese jungle crows, two Australian magpies, two Indian mynah, three zebra finches (all Passeriformes, one Southern lapwing (Charadriiformes and one monk parakeet (Psittaciformes. Microscopic survey of the brain tissue suggests that the largest PGCs are located in the hyperpallium densocellulare and mesopallium. No clusters were found in brain sections from one Gruiform (purple swamphen, one Strigiform (barn owl, one Trochiliform (green-backed firecrown, one Falconiform (chimango caracara, one Columbiform (pigeon and one Galliform (chick. Our observations suggest that PGCs in Aves are brain region- and taxon-specific and that the presence of perineuronal glia in healthy human brains and the similar PGCs in avian gray matter is the result of convergent evolution. The

  16. Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. I. Preferential labeling of glial cells on the presynaptic side

    International Nuclear Information System (INIS)

    Alpha-scorpion toxins bind specifically to the voltage-sensitive sodium channel in excitable membranes, and binding is potential-dependent. The radioiodinated toxin II from the scorpion Androctonus australis Hector (alpha ScTx) was used to localize voltage-sensitive sodium channels on the presynaptic side of mouse neuromuscular junctions (NMJ) by autoradiography using both light and electron microscopy. Silver grain localization was analyzed by the cross-fire method. At the light-microscopic level, grain density over NMJ appeared 6-8x higher than over nonjunctional muscle membrane. The specificity of labeling was verified by competition/displacement with an excess of native alpha ScTx. Labeling was also inhibited by incubation in depolarizing conditions, showing its potential-dependence. At the electron-microscopic level, analysis showed that voltage-sensitive sodium channels labeled with alpha ScTx were almost exclusively localized on membranes, as expected. Due to washout after incubation, appreciable numbers of binding sites were not found on the postsynaptic membranes. However, on the presynaptic side, alpha ScTx-labeled voltage-sensitive sodium channels were localized on the membrane of non-myelin-forming Schwann cells covering NMJ. The axonal presynaptic membrane was not labeled. These results show that voltage-sensitive sodium channels are present on glial cells in vivo, as already demonstrated in vitro. It is proposed that these glial channels could be indirectly involved in the ionic homeostasis of the axonal environment

  17. Energy-Momentum in viscous Kasner-type Universe in Bergmann-Thomson Formulations

    OpenAIRE

    Salti, Mustafa; Havare, Ali

    2005-01-01

    This paper has been removed by arXiv administrators because it plagiarizes gr-qc/0303034, "The energy of the universe in teleparallel gravity," by T. Vargas; and gr-qc/0011027, "Viscous cosmologies in scalar-tensor theories for Kasner type metrics," by M. Cataldo, S. del Campo and P. Salgado.

  18. Effect of erhuangfang on cerebral and spinal demyelination and regeneration as well as expression of glial fibrillary acidic protein in rats with experimental allergic encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    ventricle) and spinal cord (cervical enlargement and lumbar enlargement) collections,and then haematine-eosin (HE) staining and SLG myelin staining were used to observe demyelination and regeneration; meanwhile, immunohistochemical staining was used to observe the expression of glial fibriliary acidic protein (GFAP).MAIN OUTCOME MEASURES: Cerebral and spinal demyelination and regeneration as well as expression of GFAP in EAE rats.RESULTS: All 70 Lewis rats were involved in the final analysis. ① Demyelination and regeneration:Infiltration of inflammatory cells surrounding cerebrum and small venous vessels of spinal cord white matter,demyelination surrounding vessels and plentiful foam cells at myelinolysis sites were observed in the model group. Symptoms were relieved in the western medicine group and the Chinese herb group as compared with those in the model group. While, numbers of inflammatory infiltrated cells and vascular cuffs were decreased in focal region as compared with those in the model group; in addition, areas of softening focus and demyelination were decreased. ② Expression of GFAP: Volumes and numbers of positive cells of GFAP in white matter region were respectively bigger and higher than those of normal cells in the model group.Plentiful positive cells of GFAP were disorderly aggregated in hippocampus and surrounding small vessel cuffs. While, expression of GFAP was mildly increased surrounding focus in the Chinese herb group;however, GFAP did not express surrounding focus in the western medicine group. In addition, expressions of GFAP were not increased in non-focal region in both Chinese herb group and western medicine group.CONCLUSION: Both erhuangfang and hormone can relieve inflammatory reaction of central nervous system and demyelination of EAE rats. On one hand, erhuangfang can regulate reaction of astrocyte in two ways, relieve reaction and proliferation of astrocyte in non-focal region and maintain the protective effect of astrocyte on brain

  19. Glial cell-derived neurotrophic factor mRNA expression in a rat model of spinal cord injury following bone marrow stromal cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Lei Li; Gang Lü; Yanfeng Wang; Hong Gao; Xin Xu; Lunhao Bai; Huan Wang

    2008-01-01

    BACKGROUND: Several animal experiments utilizing bone marrow stromal cell (BMSC) transplantation for the treatment of spinal cord injury have proposed a hypothesis that BMSC transplantation effects are associated with increased glial cell-derived neurotrophic factor (GDNF) expression.OBJECTIVE: To confirm the effects of BMSC transplantation on GDNF mRNA expression in rats with spinal cord injury by reverse transcription-polymerase chain reaction (RT-PCR).DESIGN, TIME AND SETTING: The present molecular, cell biology experiment was performed at the Key Laboratory of Children's Congenital Malformation, Ministry of Health of China & Department of Developmental Biology, Basic Medical College, China Medical University between March 2006 and May 2007.MATERIALS: Sixty healthy Wistar rats aged 2--4-months and of either gender were included in this study. Spinal cord injury was induced in all rats by hemisection ofT9 on the left side. RT-PCR kits were purchased from TaKaRa Company, China. Type 9600 RCR amplifier was provided by PerkinElmer Company, USA. METHODS: Three rats were selected for BMSC culture and subsequent transplantation (after three passages). Of the remaining 57 rats, nine were selected for sham-operation (sham-operated group), where only the T9 spinal cord was exposed without hemisection. A total of 48 rats were randomly and evenly divided into BMSC transplantation and model groups. In the BMSC transplantation group, following spinal cord injury induction, each rat was administered a BMSC suspension through two injection sites selected on the gray and white matter boundary caudally and cephalically, seperately and near to injury site in the spinal cord. The model group received an equal volume of PBS through the identical injection sites.MAIN OUTCOME MEASURES: At 24 and 72 hours, as well as at 7 days, following spinal cord injury, the spinal cord at the T9 segment was removed. Eight rats were allocated to each time point in the BMSC transplantation and model

  20. Astrócitos imunorreativos à proteína glial fibrilar ácida (GFAP) em sistema nervoso central de equinos normais e de equinos com leucoencefalomalácia

    OpenAIRE

    Lemos Karen Regina; Alessi Antonio Carlos

    1999-01-01

    A proteína glial fibrilar ácida (GFAP), subunidade dos filamentos intermediários do citoesqueleto celular, está presente no citoplasma de astrócitos. Técnicas imunohistoquímicas com anticorpos primários anti-GFAP são geralmente empregadas para identificar astrócitos no sistema nervoso, permitindo verificar também sua hipertrofia. Vários estudos mostram a distribuição, a morfologia e a citoarquitetura de astrócitos em várias regiões do SNC do homem e de animais de laboratório. No entanto, em a...

  1. Temporal changes in glial fibrillary acidic protein messenger RNA and [{sup 3}H]PK11195 binding in relation to imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Craven, J.A.; Gundlach, A.L.; Conway, E.L. [The University of Melbourne, Clinical Pharmacology and Therapeutics Unit (Australia); Department of Medicine, Austin and Repatriation Medical Centre (Australia)

    1997-10-24

    Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [{sup 3}H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I{sub 2}-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from {alpha}{sub 2}-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [{sup 3}H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [{sup 3}H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I{sub 2}-receptor binding sites detected using the specific radioligand, [{sup 3}H]2

  2. Measurements of diagnostic examination performance and correlation analysis using microvascular leakage, cerebral blood volume, and blood flow derived from 3T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in glial tumor grading

    International Nuclear Information System (INIS)

    To assess the diagnostic accuracy of microvascular leakage (MVL), cerebral blood volume (CBV) and blood flow (CBF) values derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MR imaging) for grading of cerebral glial tumors, and to estimate the correlation between vascular permeability/perfusion parameters and tumor grades. A prospective study of 79 patients with cerebral glial tumors underwent DSC-MR imaging. Normalized relative CBV (rCBV) and relative CBF (rCBF) from tumoral (rCBVt and rCBFt), peri-enhancing region (rCBVe and rCBFe), and the value in the tumor divided by the value in the peri-enhancing region (rCBVt/e and rCBFt/e), as well as MVL, expressed as the leakage coefficient K2 were calculated. Hemodynamic variables and tumor grades were analyzed statistically and with Pearson correlations. Receiver operating characteristic (ROC) curve analyses were also performed for each of the variables. The differences in rCBVt and the maximum MVL (MVLmax) values were statistically significant among all tumor grades. Correlation analysis using Pearson was as follows: rCBVt and tumor grade, r = 0.774; rCBFt and tumor grade, r = 0.417; MVLmax and tumor grade, r = 0.559; MVLmax and rCBVt, r = 0.440; MVLmax and rCBFt, r = 0.192; and rCBVt and rCBFt, r = 0.605. According to ROC analyses for distinguishing tumor grade, rCBVt showed the largest areas under ROC curve (AUC), except for grade III from IV. Both rCBVt and MVLmax showed good discriminative power in distinguishing all tumor grades. rCBVt correlated strongly with tumor grade; the correlation between MVLmax and tumor grade was moderate. (orig.)

  3. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures

    Directory of Open Access Journals (Sweden)

    Studzinski Diane

    2009-01-01

    Full Text Available Abstract Background Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS in multiple sclerosis (MS. Methods We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M. Results In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, including neurotrophins, growth factors and structural proteins. In this paper, we present the effects of the cytokines on molecules involved in metabolism, signaling and regulatory mechanisms in CNS glia. Many of the changes in gene expression were similar to those seen in ischemic preconditioning and in early inflammatory lesions in experimental autoimmune encephalomyelitis (EAE, related to ion homeostasis, mitochondrial function, neurotransmission, vitamin D metabolism and a variety of transcription factors and signaling pathways. Among the most prominent changes, all three cytokine mixtures markedly downregulated the dopamine D3 receptor, while Th1 and Th2 cytokines downregulated neuropeptide Y receptor 5. An unexpected finding was the large number of changes related to lipid metabolism, including several suggesting a switch from diacylglycerol to phosphatidyl inositol mediated signaling pathways. Using QRT-PCR we validated the results for regulation of genes for iNOS, arginase and P glycoprotein/multi-drug resistance protein 1 (MDR1 seen at 6 hours with microarray. Conclusion Each of the three cytokine mixtures differentially regulated gene expression related to metabolism and signaling that may play roles in the pathogenesis of MS, most notably with regard to mitochondrial function and neurotransmitter

  4. Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway.

    Science.gov (United States)

    Ciccarelli, Renata; D'Alimonte, Iolanda; Santavenere, Clara; D'Auro, Mariagrazia; Ballerini, Patrizia; Nargi, Eleonora; Buccella, Silvana; Nicosia, Simonetta; Folco, Giancarlo; Caciagli, Francesco; Di Iorio, Patrizia

    2004-09-01

    Cysteinyl-leukotrienes (cys-LTs), potent mediators in inflammatory diseases, are produced by nervous tissue, but their cellular source and role in the brain are not very well known. In this report we have demonstrated that rat cultured astrocytes express the enzymes (5'-lipoxygenase and LTC(4) synthase) required for cys-LT production, and release cys-LTs in resting condition and, to a greater extent, in response to calcium ionophore A23187, 1 h combined oxygen-glucose deprivation or 2-methyl-thioATP, a selective P2Y(1)/ATP receptor agonist. MK-886, a LT synthesis inhibitor, prevented basal and evoked cys-LT release. In addition, 2-methyl-thioATP-induced cys-LT release was abolished by suramin, a P2 receptor antagonist, or by inhibitors of ATP binding cassette proteins involved in cys-LT release. We also showed that astrocytes express cys-LT(1) and not cys-LT(2) receptors. The stimulation of these receptors by LTD(4) activated the mitogen-activated protein kinase (MAPK) pathway. This effect was: (i) insensitive to inhibitors of receptor-coupled Gi protein (pertussis toxin) or tyrosine kinase receptors (genistein); (ii) abolished by MK-571, a cys-LT(1) selective receptor antagonist, or PD98059, a MAPK inhibitor; (iii) reduced by inhibitors of calcium/calmodulin-dependent kinase II (KN-93), Ca(2+)-dependent and -independent (GF102903X) or Ca(2+)-dependent (Gö6976) protein kinase C isoforms. LTD(4) also increased astrocyte proliferation and glial fibrillary acidic protein content, which are considered hallmarks of reactive astrogliosis. Both effects were counteracted by cell pretreatment with MK-571 or PD98059. Thus, cys-LTs released from astrocytes might play an autocrine role in the induction of reactive astrogliosis that, in brain injuries, contributes to the formation of a reparative glial scar. PMID:15355318

  5. Effect of GSM-1800 and U.M.T.S. exposures on micro-glial activation and heat shock proteins induction in brain: a study on young adult and elderly rats

    International Nuclear Information System (INIS)

    Contradictory results have emerged from recent studies describing low -level radiofrequency radiation (R.F.R.) as a hazardous factor for the central nervous system while others described such type of exposure as totally safe. In the brain, heat shock proteins (H.s.p.) are often induced under harmful conditions such as ischemia, traumatic injury, epilepsy, hyperthermia, drug administration, and neuro-degenerative diseases. Under those conditions, activation of the micro-glial cell population is often observed. In this work we studied the effect of two types of mobile phone signals, GSM-1800 and U.M.T.S. on the expression of two major H.s.p., induced in the brain under harmful conditions, H.s.p. 70 and H.s.p. 25. We also studied micro-glial activation in young adult (8 weeks) and elderly (17 months) Wistar rats. Height animals by group were exposed. Exposures were performed using a brain-averaged S.A.R. of 2 W/kg following two types of protocols: an acute exposure, with exposure lasting only two hours, and a sub chronic exposure in which the animals were exposed for two hours per day, five days per week, during four weeks. In all cases, rats were progressively habituated to the exposure setup (rockets) over two weeks to avoid stress and a sham group was exposed for each condition. Positive controls were performed by induction of a status epilepticus using a subcutaneous injection kainic acid (10 mg/kg). At the end of exposure, rats were anesthetized with isofluran and perfused from the heart with P.B.S. then paraformaldehyde prior to removing of the brain. Sections (10 m m thick) were prepared on slides for immunohistochemistry. Brain samples were coded and the analysis was performed in a blind manner. The sections were immuno-histo-chemically stained with antibodies raised in rabbits against H.s.p.25 and against the inducible form of H.s.p.70. The whole glial cell population was detected by its common cell surface glyco conjugates, which bind the plant Griffonia

  6. ALS-linked SOD1 in glial cells enhances ß-N-Methylamino L-Alanine (BMAA-induced toxicity in Drosophila [v1; ref status: indexed, http://f1000r.es/S4BZRP

    Directory of Open Access Journals (Sweden)

    Rafique Islam

    2012-11-01

    Full Text Available Environmental factors have been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS. However, the role of environmental agents in ALS remains poorly understood. To this end, we used transgenic fruit flies (Drosophila melanogaster to explore the interaction between mutant superoxide dismutase 1 (SOD1 and chemicals such as ß-N-methylamino L-alanine (BMAA, the herbicide agent paraquat, and superoxide species. We expressed ALS-linked human SOD1 (hSOD1A4V, and hSOD1G85R, hSOD1wt as well as the Drosophila native SOD1 (dSOD1 in motoneurons (MNs or in glial cells alone and simultaneously in both types of cells. We then examined the effect of BMAA (3 mM, paraquat (20 mM, and hydrogen peroxide (H2O2, 1% on the lifespan of SOD1-expressing flies. Our data show that glial expression of mutant and wild type hSOD1s reduces the ability of flies to climb. Further, we show that while all three chemicals significantly shorten the lifespan of flies, mutant SOD1 does not have a significant additional effect on the lifespan of flies fed on paraquat, but further shortens the lifespan of flies fed on H2O2. Finally, we show that BMAA shows a dramatic cell-type specific effect with mutant SOD1. Flies with expression of mutant hSOD1 in MNs survived longer on BMAA compared to control flies. In contrast, BMAA significantly shortened the lifespan of flies expressing mutant hSOD1 in glia. Consistent with a neuronal protection role, flies expressing these mutant hSOD1s in both MNs and glia also lived longer. Hence, our studies reveal a synergistic effect of mutant SOD1 with H2O2 and novel roles for mutant hSOD1s in neurons to reduce BMAA toxicity and in glia to enhance the toxicity of BMAA in flies.

  7. 应用CATS法分离和鉴定猪GFAP基因的研究%Isolation and Characterization of the Porcine Glial Fibrillary Acidic Protein ( GFAP) Gene by CATS

    Institute of Scientific and Technical Information of China (English)

    余梅; 李奎; 赵书红; 刘榜; 熊统安

    2001-01-01

    Primers for the glial fibrillary acidic protein (GFAP) gene weredesigned from a human cDNA sequence aligned with the mouse GFAP gene on the principle of comparative anchor tagged sequence (CATS). The 412bp PCR product isolated from Chinese Erhualian pig genome was characterized as the porcine GFAP gene by comparing the sequence with the GenBank database. The chromosomal location of the GFAP gene is on pig Chr: 12(p11-(2/3)p13) using pig×rodent somatic cell hybrid panel.%根据比较锚定序列示踪(CATS)法,选择人和小鼠胶质细胞原纤维酸性蛋白(GFAP)基因的同源区域设计引物,用PCR方法从二花脸猪基因组中分离到412bp的基因片段,经与基因资料库中已知功能基因的同源性比较,该片段可鉴定为猪的GFAP基因,利用猪-啮齿类体细胞杂种克隆板将CFAP基因定位于猪12号染色体12p11-(2/3)p13区域。

  8. Glial fibrillary acidic protein (GFAP) immunoreactivity correlates with cortical perfusion parameters determined by bolus tracking arterial spin labelling (bt-ASL) magnetic resonance (MR) imaging in the Wistar Kyoto rat.

    Science.gov (United States)

    Gormley, Shane; Rouine, Jennifer; McIntosh, Allison; Kerskens, Christian; Harkin, Andrew

    2016-06-01

    Alterations in astrocyte number and function have been implicated in the pathophysiology of a number of psychiatric disorders. The development of magnetic resonance imaging (MRI) as a tool in the animal laboratory has enabled an investigation of the relationship between pathological and neuroimaging markers in animal models. However the physiological processes which underlie these markers and their role in mediating behavioural deficits is still poorly understood. Rodent models have provided us with important insights into physiological and cellular mechanisms which may mediate anxiety and depression-related behaviours. The Wistar-Kyoto (WKY) rat is a strain which endogenously expresses highly anxious and depressive-like behaviours and has previously been reported to exhibit alterations in immunoreactivity for the astrocytic marker glial fibrillary acidic protein (GFAP) in brain sub-regions relative to more stress resilient out-bred strains. Here we report that the depressive and anxiety-like behaviours exhibited by the WKY rat strain are associated with alterations in brain morphology including a decrease in hippocampal volume, coupled with reduced resting state frontal cortical perfusion as assessed by MR bolus tracking arterial spin labelling (bt-ASL) relative to the out-bred Wistar strain. Pre-limbic cortical GFAP immunoreactivity and astrocyte cell number were positively correlated with cortical blood perfusion in the WKY strain. These experiments provide a link between pathological and neuroimaging markers of aberrant astrocytic function and add validity to the WKY rat as a model for co-morbid anxiety and depression. PMID:27068181

  9. The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

    Directory of Open Access Journals (Sweden)

    Nadarajah Vishna

    2011-03-01

    Full Text Available Abstract Background Chlorpyrifos (CPF, a commonly used pesticide worldwide, has been reported to produce neurobehavioural changes. Dermal exposure to CPF is common in industries and agriculture. This study estimates changes in glial fibrillary acidic protein (GFAP expression in hippocampal regions and correlates with histomorphometry of neurons and serum cholinesterase levels following dermal exposure to low doses of CPF with or without swim stress. Methods Male albino mice were separated into control, stress control and four treatment groups (n = 6. CPF was applied dermally over the tails under occlusive bandage (6 hours/day at doses of 1/10th (CPF 0.1 and 1/5th dermal LD50 (CPF 0.2 for seven days. Consequent treatment of swim stress followed by CPF was also applied. Serum cholinesterase levels were estimated using spectroflurometric methods. Paraffin sections of the left hippocampal regions were stained with 0.2% thionin followed by the counting of neuronal density. Right hippocampal sections were treated with Dako Envision GFAP antibodies. Results CPF application in 1/10th LD50 did not produce significant changes in serum cholinesterase levels and neuronal density, but increased GFAP expression significantly (p Conclusions Findings suggest GFAP expression is upregulated with dermal exposure to low dose of CPF. Stress combined with sub-toxic dermal CPF exposure can produce neurotoxicity.

  10. C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain.

    Science.gov (United States)

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2015-08-01

    Spirulina is a widely used health supplement and is a dietary source of C-Phycocyanin (CPC), a potent anti-oxidant. We have previously reported the neurotoxic potential of tributyltin chloride (TBTC), an environmental pollutant and potent biocide. In this study, we have evaluated the protective efficacy of CPC against TBTC induced neurotoxicity. To evaluate the extent of neuroprotection offered by CPC, its efficacy was compared with the degree of protection offered by N-acetylcysteine (NAC) (a well known neuroprotective drug, taken as a positive control). Male Wistar rats (28 day old) were administered with 20mg/kg TBTC (oral) and 50mg/kg CPC or 50mg/kg NAC (i.p.), alone or in combination, and various parameters were evaluated. These include blood-brain barrier (BBB) damage; redox parameters (ROS, GSH, redox pathway associated enzymes, oxidative stress markers); inflammatory, cellular, and stress markers; apoptotic proteins and in situ cell death assay (TUNEL). We observed increased CPC availability in cortical tissue following its administration. Although BBB associated proteins like claudin-5, p-glycoprotein and ZO-1 were restored, CPC/NAC failed to protect against TBTC induced overall BBB permeability (Evans blue extravasation). Both CPC and NAC remarkably reduced oxidative stress and inflammation. NAC effectively modulated redox pathway associated enzymes whereas CPC countered ROS levels efficiently. Interestingly, CPC and NAC were equivalently capable of reducing apoptotic markers, astroglial activation and cell death. This study illustrates the various pathways involved in CPC mediated neuroprotection against this environmental neurotoxicant and highlights its capability to modulate glial cell activity. PMID:26079211

  11. Marcação imunoistoquímica da expressão astrocitária de proteína glial fibrilar ácida e de vimentina no sistema nervoso central de cães com cinomose Immunohistochemical staining of the astrocytic expression of glial fibrillary acidic protein and vimentin in the central nervous system of dogs with canine distemper

    Directory of Open Access Journals (Sweden)

    Heloísa Orsini

    2007-12-01

    Full Text Available Uma vez que muitos dos aspectos envolvidos na patogenia dos processos desmielinizantes do sistema nervoso central (SNC são ainda pouco esclarecidos e que os astrócitos parecem estar envolvidos na mediação de tais processos, este estudo analisou morfologicamente a participação astrocitária na desmielinização do SNC por meio da marcação imunoistoquímica de duas proteínas dos filamentos intermediários astrocitários - a proteína glial fibrilar ácida (GFAP e a vimentina (VIM -, comparando amostras de cerebelo e de tronco encefálico de oito cães com cinomose e de dois cães normais, de diferentes raças e com idades entre um e quatro anos. Cortes histológicos dos tecidos foram submetidos à marcação pelo método indireto da avidina-biotina-peroxidase (ABC e a reatividade astrocitária, observada em microscopia de luz, foi quantificada em um sistema computacional de análise de imagens. Observou-se, na maioria dos cortes de animais doentes, a presença de lesões degenerativas compatíveis com desmielinização. A marcação para a GFAP e para a VIM foi mais intensa nos animais com cinomose do que nos animais normais, especialmente nas regiões circunventriculares e nas adjacentes às áreas de degeneração tecidual. Não houve diferença significativa entre a imunomarcação (GFAP e VIM dos animais com cinomose com e sem infiltração inflamatória da substância branca do cerebelo. O aumento da imunorreatividade dos astrócitos para a GFAP e a reexpressão de VIM nas áreas lesionais indicam o envolvimento astrocitário na resposta do tecido nervoso às lesões desmielinizantes induzidas pelo vírus da cinomose (CDV no SNC.Considering that many aspects involved in the pathogenesis of the central nervous system (CNS demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using

  12. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer's disease (AD) and in primary human neuronal-glial (HNG) cells.

    Science.gov (United States)

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, Jim; Dua, Prerna; Lukiw, Walter J

    2014-08-01

    Inducible microRNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health, and disease. Using miRNA arrays, RNA sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot, and bioinformatics analysis, we have studied miRNA abundance and complexity in Alzheimer's disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells, we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is among the most abundant and significantly induced miRNA species in human brain cells and tissues. Bioinformatics analysis indicated that an up-regulated miRNA-125b could potentially target the 3'untranslated region (3'-UTR) of the messenger RNA (mRNA) encoding (a) a 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized in the conversion of docosahexaneoic acid into neuroprotectin D1 (NPD1), and (b) the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid-mediated signaling, neurotrophic support, defense against reactive oxygen and nitrogen species (reactive oxygen and nitrogen species), and neuroprotection in the CNS. Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3'-UTR region of the 15-LOX and VDR messenger RNAs (mRNAs). In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation and a deficiency in neurotrophic support may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b. We will review the recent data on the pathogenic actions of this up-regulated miRNA-125b in AD and discuss potential

  13. Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty

    International Nuclear Information System (INIS)

    Maternal smoking during pregnancy is known to be a significant contributor to developmental neurological health problems in the offspring. In animal studies, nicotine treatment via injection during gestation has been shown to produce episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady level of nicotine in the plasma. In the present study timed-pregnant Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, were evaluated for changes in the ligand binding for various types of nicotinic acetylcholine receptors and neuropathological alterations. Neurobehavioral evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline plane and grip time response were carried out on PND 60 offspring. Beam-walk time and forepaw grip time showed significant impairments in both male and female offspring. Ligand binding densities for [3H]epibatidine, [3H]cytisine and [3H]α-bungarotoxin did not show any significant changes in nicotinic acetylcholine receptors subtypes in the cortex at PND 30 and 60. Histopathological evaluation using cresyl violet staining showed significant decrease in surviving Purkinje neurons in the cerebellum and a decrease in surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer of cerebellum and the CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. These results indicate that maternal exposure to nicotine produces significant neurobehavioral deficits, a decrease in the surviving neurons and an

  14. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.

    Science.gov (United States)

    Welch, Robert D; Ayaz, Syed I; Lewis, Lawrence M; Unden, Johan; Chen, James Y; Mika, Valerie H; Saville, Ben; Tyndall, Joseph A; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C; Schmid, Kara; Hayes, Ronald L; Vossough, Arastoo; Sweriduk, Stephen T; Bazarian, Jeffrey J

    2016-01-15

    Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555

  15. Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

    Directory of Open Access Journals (Sweden)

    Rodnight R.

    1997-01-01

    Full Text Available The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP, in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca2+-dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR. Since group II mGluRs do not act by liberating Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ entry into the astrocytes and consequently down-regulates a Ca2+-dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during

  16. Conditionally replicative adenovirus under the control of glial fibrillary acidic protein and human telomerase reverse transcriptase dual-promoters direct sodium iodide symporter expression for malignant glioma radioiodine therapy

    International Nuclear Information System (INIS)

    Objective: To explore the possibility of using 131I as a targeted therapy method for malignant glioma by infecting U87 and U251 cells with conditionally replicative adenovirus Ad-Tp-E1a-Gp-NIS. Methods: Human telomerase reverse transcriptase (hTERT) promoter and glial fibrillary acidic protein (GFAP) promoter were cloned and their transcriptional activities were detected by luciferase assay. The conditionally replicative adenovirus Ad-Tp-E1 a-Gp-NIS was constructed,purified,and transfected into U87 and U251 glioma cells. For these transfected cells, the selective replication ability was evaluated by plaque forming assay, and protein expression was detected by Western blot assay. 125I-iodide uptake and exflux, the clone formation of 131I-iodide treated cells were also measured. Results: Transcriptions activity of the GFAP and hTERT promoters was 59.75%-62.10% (F = 11.89, P < 0.01) in U87 cells and 37.31%-49.00% (F = 5.87, P < 0.05) in U251 cells. The Ad-Tp-E1a-Gp-NIS could be selectively replicated and the hNIS gene was successfully expressed in the hTERT-positive and GFAP-positive glioma cells which showed two protein bands with relative molecular mass of 120 × 103 and 49 × 103 in Western blot assay. After infection with Ad-Tp-E1a-Gp-NIS, the cell ability of 125I uptake was increased by 78.80 (F = 2 914.58, P <0.01) and 92.48 (F = 2 275.91, P <0.01) times in U87 and U251 cells, respectively. The GFAP-negative MRC-5 cells could not take in 125I. The in vitro clonogenic assay indicated that, after 131I treatment, more than 90% of the transfected cells were killed, while only about 65% (t = 11.73-78.33, P < 0.01) of control cells were killed. Conclusions: The Ad-Tp-E1a-Gp-NIS has a good ability in selective replication and the enhancement of antitumor therapy effect by increasing tumor-specific iodide uptake in malignant glioma cells. (authors)

  17. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells

    Science.gov (United States)

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M.; Hill, Jim; Dua, Prerna; Lukiw, Walter J.

    2014-01-01

    Inducible micro RNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health and disease. Using miRNA arrays, RNA-sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot and bioinformatics analysis we have studied miRNA abundance and complexity in Alzheimer’s disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is amongst the most abundant and significantly induced miRNA species in human brain cells and tissues. Bioinformatics analysis indicates that up-regulated miRNA-125b targeted expression of (a) the 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized in the conversion of docosa-hexaneoic acid (DHA) into neuroprotectin D1 (NPD1), and (b) the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid-mediated signaling, neurotrophic support, defense against reactive oxygen and nitrogen species (ROS, RNS) and neuroprotection in the CNS. Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3′-untranslated region (3′-UTR) of the 15-LOX and VDR messenger RNAs (mRNAs). In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation and a deficiency in neurotrophic support, may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b. We will review recent data on the pathogenic actions of this up-regulated miRNA-125b in AD, and discuss potential therapeutic approaches using either anti-NF-kB or anti-miRNA-125b strategies. These may

  18. Imaging micro-glial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by Positron Emission Tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714

    International Nuclear Information System (INIS)

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated micro-glia/macrophages play a key role in the immuno-pathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Micro-glia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of micro-glial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuro-inflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl) - isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuro-inflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuro-inflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuro-inflammation for detection, monitoring, and research in MS. (authors)

  19. Franziska Bergmann, Franziska Schößler, Bettina Schreck (Hg.: Gender Studies. Bielefeld: transcript Verlag 2012.

    Directory of Open Access Journals (Sweden)

    Sophia Gayana Ermert

    2013-05-01

    Full Text Available In Form eines Readers führen die Herausgeberinnen in einflussreiche Theorien, Schlüsselbegriffe und Texte der Gender Studies ein. Dabei sollen explizit Kanonisierungstendenzen dargestellt werden, wie sie sich an deutschen Universitäten entwickelt haben, und diese durch bedeutende Texte aus den USA ergänzt werden. So ist eine spannende Textauswahl entstanden; Theorien und Begriffe werden verständlich erläutert. Kritische Fragen nach Ausschlüssen von Ansätzen oder Texten durch Kanonisierung sowie nach der strukturellen Bedeutung von Inter- bzw. Transdisziplinarität für die Gender Studies werden jedoch leider nicht gestellt.The editors of this anthology introduce influential theories, key terms, and texts of the field of gender studies. In doing so, they explicitly want to illustrate tendencies of canonization as they have developed at German universities and complement these with significant texts from the USA. This approach leads to an exciting choice of texts. Theories and terms are explained comprehensibly. Unfortunately however, the anthology does not ask critical questions regarding the exclusion of approaches or texts through canonization as well as critical questions regarding the structural relevance of inter- and transdisciplinarity for gender studies.

  20. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

    OpenAIRE

    Ango, Fabrice; Wu, Caizhi; van der Want, Johannes; Wu, Priscilla; Schachner, Melitta; Huang, Z. Josh

    2008-01-01

    Author Summary Large principal neurons in vertebrate neural circuits often consist of distinct anatomical and physiological compartments, which allow distributed and compartmentalized signaling and greatly increase the computational power of single neurons. Superimposed upon this intrinsic compartmental architecture is the subcellular organization of synaptic inputs, which exert local control over the biophysical properties and differentially regulate the input, integration, and output of pri...

  1. Testing Bergmann's rule and the resource seasonality hypothesis in Malagasy primates using GIS-based climate data.

    Science.gov (United States)

    Kamilar, Jason M; Muldoon, Kathleen M; Lehman, Shawn M; Herrera, James P

    2012-03-01

    We tested four major hypotheses on the ecological aspects of body mass variation in extant Malagasy strepsirrhines: thermoregulation, resource seasonality/scarcity, resource quality, and primary productivity. These biogeographic hypotheses focus on the ecological aspects of body mass variation, largely ignoring the role of phylogeny for explaining body mass variation within lineages. We tested the independent effects of climate and resource-related variables on variation in body mass among Malagasy primates using recently developed comparative methods that account for phylogenetic history and spatial autocorrelation. We extracted data on lemur body mass and climate variables for a total of 43 species from 39 sites. Climatic data were obtained from the WorldClim database, which is based on climate data from weather stations compiled around the world. Using generalized linear models that incorporate parameters to account for phylogenetic and spatial autocorrelation, we found that diet and climate variables were weak predictors of lemur body mass. Moreover, there was a strong phylogenetic effect relative to the effects of space on lemur body mass in all models. Thus, we failed to find support for any of the four hypotheses on patterns of geography and body mass in extant strepsirrhines. Our results indicate that body mass has been conserved since early in the evolutionary history of each genus, while species diversified into different environmental niches. Our findings are in contrast to some previous studies that have suggested resource and climate related effects on body mass, though these studies have examined this question at different taxonomic and/or geographic scales. PMID:22271559

  2. Glial cells in familial amyloidotic polyneuropathy

    OpenAIRE

    Gonçalves, Nádia Pereira; Costelha, Susete; Saraiva, Maria João

    2014-01-01

    Introduction Transthyretin V30M mutation is the most common variant leading to Familial Amyloidotic Polyneuropathy. In this genetic disorder, Transthyretin accumulates preferentially in the extracellular matrix of peripheral and autonomic nervous systems leading to cell death and dysfunction. Thus, knowledge regarding important biological systems for Transthyretin clearance might unravel novel insights into Familial Amyloidotic Polyneuropathy pathophysiology. Herein, our aim was to evaluate t...

  3. NMDA Receptors in Glial Cells: Pending Questions

    Czech Academy of Sciences Publication Activity Database

    Džamba, Dávid; Honsa, Pavel; Anděrová, Miroslava

    2013-01-01

    Roč. 11, č. 3 (2013), s. 250-262. ISSN 1570-159X R&D Projects: GA ČR GA309/08/1381; GA ČR(CZ) GBP304/12/G069 Grant ostatní: GA UK(CZ) 604212 Institutional support: RVO:68378041 Keywords : astrocytes * ischemia * NMDA receptors Subject RIV: FH - Neurology Impact factor: 2.347, year: 2013

  4. Pathway Analyses Implicate Glial Cells in Schizophrenia

    OpenAIRE

    Duncan, Laramie E.; Holmans, Peter A.; Lee, Phil H.; O'Dushlaine, Colm T; Kirby, Andrew W.; Smoller, Jordan W.; Öngür, Dost; Cohen, Bruce M.

    2014-01-01

    Background: The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge. Method Ten publically available gene sets (pathwa...

  5. Physiology of neuronal-glial networking

    Czech Academy of Sciences Publication Activity Database

    Verkhratsky, Alexei

    2010-01-01

    Roč. 57, č. 4 (2010), s. 332-343. ISSN 0197-0186 Institutional research plan: CEZ:AV0Z50390703 Keywords : Glia * Astrocytes * Glutamate receptors Subject RIV: FH - Neurology Impact factor: 3.601, year: 2010

  6. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.; Pakkenberg, B.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  7. Sonic hedgehog patterning during cerebellar development.

    Science.gov (United States)

    De Luca, Annarita; Cerrato, Valentina; Fucà, Elisa; Parmigiani, Elena; Buffo, Annalisa; Leto, Ketty

    2016-01-01

    The morphogenic factor sonic hedgehog (Shh) actively orchestrates many aspects of cerebellar development and maturation. During embryogenesis, Shh signaling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Shh secreted by Purkinje cells sustains the amplification of postnatal neurogenic niches: the external granular layer and the prospective white matter, where excitatory granule cells and inhibitory interneurons are produced, respectively. Moreover, Shh signaling affects Bergmann glial differentiation and promotes cerebellar foliation during development. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying its role in physiological and pathological conditions. PMID:26499980

  8. Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochun Yang; Xuanchu Duan

    2013-01-01

    A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.

  9. Glial Cell Line-derived Neurotrophic Factor(GDNF):Expression,function and Mechanisms in Drug Addiction%胶质细胞源性神经营养因子的表达、功能和在药物依赖中的作用

    Institute of Scientific and Technical Information of China (English)

    陈为升; 周文华; 杨国栋

    2004-01-01

    1993年,Lin等从大鼠胶质细胞株B49中提纯到一种可促进胚胎中脑多巴胺能神经元存活的神经营养因子,并命名为胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)。GDNF和后来发现的neurturin(NRTN)、persephin(PSPN)、artemin(ARTN)在结构和功能上有很大的相似性,共同构成一个家族,称为GDNF家族。

  10. 17β-雌二醇对海马组织结构和GFAP表达的影响%Effects of 17 beta-estradiol on tissue structure and glial fibrillary acidic protein expression in hippocampus

    Institute of Scientific and Technical Information of China (English)

    吴建云; 王豪举; 王剑; 谌剑波; 张家骅

    2013-01-01

    为研究17β雌二醇对脑的保护作用机制,以去卵巢大鼠为动物模型,采用甲苯胺蓝染色、免疫组织化学染色和透射电镜技术,观察了17β-雌二醇对海马组织结构和胶质纤维酸性蛋白表达的影响.结果显示:①与对照组、假手术组和去卵巢后补充雌激素组比较,在去卵巢组中,海马CA1~3区、齿状回神经元数量显著减少(P<0.05),CA4区神经元数量减少不显著(P>0.05);海马CA1~4区、齿状回星形胶质细胞数量增加不显著(P>0.05);海马CA1~4区、齿状回胶质纤维酸性蛋白表达增加,除CA4区与去卵巢后补充雌激素组之间无显著差异外(P>0.05),其余均差异显著(P<0.05);海马CA1区神经元、胶质细胞线粒体肿胀,神经元突触和突触囊泡减少,轴突变性;②与去卵巢组比较,去卵巢后补充雌激素组海马CA1~3区、齿状回神经元数量明显增加(P<0.05);海马CA1~4区、齿状回星形胶质细胞数量减少不显著(P>0.05);海马CA1~3区、齿状回胶质纤维酸性蛋白表达显著降低(P<0.05);保持了海马CA1区神经元和胶质细胞超微结构的正常.结果表明,17β-雌二醇能通过增加神经元数量,降低星形胶质细胞胶质纤维酸性蛋白表达,保持神经元和胶质细胞正常的超微结构,实现对海马的保护.%To reveal the mechanism of protective effect of 17 beta-estradiol on the brain,the toluidine blue staining,immunohistochemistry technique and transmission electron microscope were used to investigate the effect of 17 beta-estradiol on hippocampal tissue structure and glial fibrillary acidic protein(GFAP) expression in ovariectomized rats. The result showed that, compared NC group with SHAM group and OVX+ERT group,the number of neurons in OVX group decreased significantly(P0. 05); the quantity of astrocyte changed indistinc-tively(P>0. 05) in Cal to 4 and DG;GFAP expression in OVX group remarkably increased in Cal to 4 and DG

  11. Detection of early glial responses in the retina,optic nerve and optic chiasm in acute ocular hypertension rat model%急性眼压升高所致视网膜、视神经及视交叉胶质细胞的早期反应

    Institute of Scientific and Technical Information of China (English)

    张绍丹; 李维义; 王雯倩; 黄萍; 王宁利; 张纯

    2012-01-01

    胞的反应,增生的胶质细胞表达神经前体细胞的标志物.视网膜与视神经和视交叉的改变在时间上具有一定的同步性.%Background Glial cells perform specialized function in many aspects of the development,homeostasis,and function of neurons.Retinal ganglion cells (RGCs)and glia interactions are critically important in glaucomatous neurodegeneration.However,the precise mechanisms of glial activation and ganglion cells damage are still remained unclear. Objective This study was to assess the early responses of glial cells in the retina,optic nerve and optic chiasm in rat models of acute high intraocular pressure (IOP),and to examine the expression of nestin,a neuronal progenitor marker,in the reactive glias. Methods Acute high IOP of 110 mmHg was induced in the right eyes of 6 clean adult female Wistar rats by infusing normal saline solution into the anterior chamber for 60 minutes.Three normal matched Wistar rats were used as controls.The rats were sacrificed by overanaesthesia and sections of retina,optic nerve and optic chiasm were collected on 3 days and 7 days after the injection.Rat retina was examined by Nissl staining to illustrate the gross structure changes.Loss of axons of RGCs in the optic nerve was assessed by immunostaining of β Ⅲ-tubulin.Double labeling of glia] fibrillary acidic protein (GFAP) and nestin was performed in sections of retina,optic nerve and optic chiasm to evaluate the glial responses.The use of the animals complied with Statement of Animal Ethic Committee of Peking University Third Hospital. Results In control rats,GFAP-positive glial cells were observed in the retina,optic nerve and optic chiasm,where only weak positive response for nestin was noticed.Three days after acute IOP elevation,thickness of inner plexus form layer was significantlydecreased in comparison with the control rats.A loss of 46% RGCs was found in the rats with ocular hypertension.Obvious increase of GFAP expression was

  12. 延髓缺血对其微血管密度、神经元及神经胶质细胞的影响%The changes of the microvessel density and effects of neurons and glial cells in medulla after medullary ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    朱江; 郭森; 孙艳军; 冯亚茹; 来锦

    2012-01-01

    Objective To observe the changes of the microvasculature, neurons and glial cells in rats medullas in different periods of medullary ischemia. Methods 48 healthy adult male Wistar rats (200 ~220g) were divided randomly into four groups:experimental group (one week group,two weeks group,three weeks group) and control group, 12 rats in each group. The experimental group were ligated the right common carotid artery and blocked the bilateral vertebral by elec-trocoagulation to make the medullary ischemia model. To observe the changes of the microvascular density,neurons and glial cells in rats medullas in different periods of medullary ischemia. Staining medullary microvascular with tannic acid-ferric chloride method (TA-FE method). MiVnt image analytical system was used to quantitatively analyze the microvessel density (MVD) and the microvessel area density (MVA) of medulla. HE Staining was used to investigate neurons and glial cells ( neuroglia cell) in medullary internal. Of each rat,four slices were observed. Under optical microscope at 200 times,5 visual fields were randomly chosen from each slices to count the number of neurons and glial cells. Results Animal models of different times of the experimental group showed that the microvascular density and microvascular area ratio appeared reducing trends(P <0. 05). The number of glial cells showed a continuous increasing trend(P <0. 05). Change in the number of neurons appears a decreasing trend (P <0. 05 ). Conclusion The change, neurons first increasing then reducing but glial cells increasing after the medullary ischemia,can be observed definitely in the H&E method. At the same time,the irrersible damage to the structure of neurons also can be showed clearly.%目的 观察延髓缺血后不同时段微血管、神经元、神经胶质细胞的改变.方法 雄性Wistar大鼠共48只,随机分成4组,即实验组(1w组、2w组、3w组)和对照组,每组12只.采用电凝法及丝线结扎法,阻断双侧椎动脉

  13. GFAP启动子介导放射性131Ⅰ靶向性治疗胶质瘤的实验研究%Glial fibrillary acidic protein promoters directed sodium iodide symporter expression in malignant gioma radioiodine therapy

    Institute of Scientific and Technical Information of China (English)

    李玮; 谭建; 王澎

    2013-01-01

    possibility that the glial fibrillary acidic protein (GFAP) promoters modulate the human sodium iodide symporter (hNIS) expression in glioma and lead transecting hNIS gene into glioma cells for radioactive iodide treatment.Methods PGL3-Basic,PGL3-Control and PGL3-GFAP plasmids were transfected into U251,U87 and MRC-5 cells,respectively,with the help of liposome Lipofectamine 2000; 24 h after that,the reactivity of these cells was detected and the efficiency of GFAP promoter was tested under chemiluminescence apparatus.Recombinant adenovirus vector Ad-GFAP-hNIS in which GFA P promoter could modulate the hNIS gene expression was constructed,and then,the vector was transfected into the U251,U87 and MRC-5 cells; Western blotting was employed to detect the protein expressions of GFAP and hNIS.Ad-CMV-EGFP group (blank control) and Ad-CMV-hNIS group (negative control) and Ad-GFAP-hNIS group were employed; the 125I uptake and effiux abilities and the cell amount after gentian violet staining in the three groups were measured by γ counter; the clonogenecity rate of them was calculated.BALB/c female nude mice (n=20) was divided into four groups:group of injecting Ad-GFAP-hNIS without 131I,group of injecting Ad-GFAP-hNIS with 131I,group of injecting Ad-CMV-EGFP without 131I and group of injecting Ad-CMV-EGFP with 131I (n=5);U87 cells were transfected into the nude mice,and then,the tumor growth was observed and the life cycle of the mice was noted.Nude mice bearing the U87 tumors were injected Ad-GFAP-hNIS and Ad-CMV-EGFP,followed by 1 mCi 99mTcO4 via intraperitoneal injection; single photon emission computed tomography (SPECT) was performed.Results As compared with that of cells being transfected with PGL3-blank plasmid,the relative reactivity of U251 and U87 cells being transfected with PGL3-GFAP plasmid was decreased with significant difference (P<0.05).Western blotting revealed GFAP and hNIS proteins in U87 and U251 cells.125I uptake of U87 and U251 cells after Ad

  14. Effects of Simvastatin on glial fibrillary acidic protein expression in rats with traumatic brain injury%辛伐他汀对创伤性脑损伤大鼠胶质原纤维酸性蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    靳春杰; 周伟; 江荣才; 张士俊

    2012-01-01

    目的:利用大鼠创伤性脑损伤(Traumatic brain injury,TBI)模型,探讨胶质原纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)在脑组织的表达变化规律及辛伐他汀(Simvastatin,SIM)对其的影响.方法:5周龄SD大鼠54只,随机分3组:假致伤组、对照组、治疗组,每组18只.对照组、治疗组参照Feeney氏法制造TBI模型.造模前晚及术后每晚治疗组给予SIM 10 mg/kg灌胃;对照组给予等量淀粉灌胃;于伤后3、12、24 h和3、7、14 d处死取脑.采用免疫组化技术,检测大鼠伤侧海马CA3区GFAP表达变化情况.结果:对照组伤后3h即见GFAP阳性表达增强,3、7d,GFAP阳性细胞增加达到高峰(P<0.01).治疗组伤后冶疗7d时GFAP的阳性表达较对照组明显下降(P<0.05),而治疗≤3 d和治疗14 d时,与对照组相比差异无统计学意义(P>0.05).结论:SIM可抑制GFAP在TBI后的过度表达.%Objective:To study the changing rules of glial fibrillary acidic protein(GFAP) expressions in the rat brain after traumatic brain injury(TBI) and to observe the effect of Simvastatin(SIM)on them based on the TBI rat model. Methods:Totally 54 Sprague-Dwalye(SD) rats aged 5 weeks were employed and divided into sham TBI group,control group and treatment group(n=18). TBI model was established in control group and treatment group by Feeney's method. The rats in treatment group were fed SIM 10 mg/kg in the evening pre-injury and in every evening post-injury while those in control group were fed the same dose of starch each time. Then the rats were sacrificed and the rat brains were collected at different time points(3,12,24 h and 3,7,14 d post the injury). The changes of GFAP expressions in comu ammonis(CA) area were detected with immunohistochemistry. Results :The GFAP positive cell percentage was higher in control group than in sham TBI group at 3 h after the injury. The GFAP positive cell percentage reached the peak at 3 d and 7 d after the injury (P0.05). Conclusion

  15. 次声作用对小鼠脑中胶质纤维酸性蛋白 表达和分布的影响%Expression and distribution of glial fibrillary acidic protein in the brain of the mouse exposed to infrasound

    Institute of Scientific and Technical Information of China (English)

    牟翔; 陈景藻; 李玲; 贾克勇; 邱建勇

    2001-01-01

    Objective To explore the expression and distribution of glial fibrillary acidic protein(GFAP)in the brain of the mouse exposed to infrasound. Methods The mouse exposed to infrasound of 16Hz with intensity of 130 dB for 1,7,14,21, 28 d and two hours every time in a day.They were observed with immunohistochemical technique for the expression and distribution of GFAP in the brain. Results GFAP immunoreactive cells presented mainly in the hippocampus, cortex and hypothalamus and others after being exposed for certain times. The number of GFAP immunoreactive cells grew with increasing of the time of infrasound action. Conclusion These brain regions are sensitive to infrasound and effects of infrasound can increase expression of GFAP.%目的 观察次声作用后小鼠脑中胶质纤维酸性蛋白(GFAP)的表达和分布。方法 将BALB/C小鼠暴露于16 Hz、声压130 Db次声,2 h/次.d-1,分别作用1、7、14、21和28 d后,采用免疫组织化学方法观察小鼠脑中GFAP的表达和分布。结果 次声作用一定时间后,GFAP阳性胶质细胞主要分布在海马、皮质、下丘脑等脑区,且随次声作用天数增加,GFAP阳性胶质细胞数目增多。结论 这些脑区对次声较为敏感,次声作用可导致GFAP表达增高。

  16. 季铵盐壳聚糖三维支架复合GNDF载间充质干细胞向神经样细胞分化%Neuron-like differentiation of mesenchymal stem cells induced by quaternary chitosan thermosensitive hydrogel scaffolds combined with glial cell line-derived neurotrophic factor

    Institute of Scientific and Technical Information of China (English)

    黄成; 杨建东; 冯新民; 李广峰; 李艺楠; 肖海祥; 孙钰

    2013-01-01

    chitosan thermosensitive hydrogel scaffold and to look for more ideal tissue engineering materials for the treatment of nervous system damage. METHODS:The thermosensitive hygrogel scaffold was prepared using hydroxypropyltrimethyl ammonium chloride chitosan (HACC) andβ-glycerophosphate (β-GP). The spatial structure of scaffold was observed by scanning electronic microscope. Effect of leaching liquor from the HACC/β-GP scaffold on the viability of bone marrow mesenchymal stem cells was detected by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The albumin from bovine serum was combined with the scaffold, and the slow-release effect of the scaffold was detected by ultraviolet absorption spectrometry. Bone marrow mesenchymal stem cells were incubated onto the compound scaffold at 3 passages. The adhesion, growth and differentiation of bone marrow mesenchymal stem cells on the compound scaffold were observed by the scanning electron microscope. Neuron-specific enolase was detected by immunofluorescence. RESULTS AND CONCLUSION:The porosity and thermal sensitivity of HACC/β-GP scaffold and slow-release effect of glial cellline-derived neurotrophic factor were apparent. The results of MTT showed that the compound scaffold cannot take apparent negative effects to the proliferation of bone marrow mesenchymal stem cells. After inoculation, bone marrow mesenchymal stem cells permeated the porous structure of the scaffold and adhered to the scaffold. Under the role of glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells showed neuron-like cellmorphology and cells co-cultured with the compound scaffold expressed the marker of neurons, neuron-specific enolase. Under the role of slow-release glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells can grow wel in vitro and differentiate into neuron-like cells on the HACC/β-GP scaffold.

  17. Cell apoptosis in perihematomal brain regions and expression of Caspase-3 protein in patients with hypertensive intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Xinqing Zhang; Xiaoliang Yin; Kun Zhang; Zhimin Zhang; Hui Cai; Honglan Xu

    2006-01-01

    hours) and. 5 cases in delayed phase(onset > 24 hours). The brain tissue obtained from distant regions of hematoma was preserved for control group (5 cases). ②All the specimens were subjected to terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) staining and Caspase-3 immunohistochemical staining. The change rule of positive cells was observed with image analyzer, and the relationship between apoptotic cells and Caspase-3 positive cells was analyzed. ③ Analysis of variance and t test were used for comprising the difference of measurement data, and liner correlation analysis was performed. MAIN OUTCOME MEASURES: ①Changes of cell apoptosis and Caspase-3 expression in brain tissue of perihematomal region of HICH patents in different phases. ② Correlation of cell apoptosis and Caspase-3 expression.RESULTS: Cell apoptosis: TUNEL positive cells were hardly or occasionally found in each visual field in the control group, while the number of apoptotic cells in 3 different phases in the patient group was all higher than that of control group, and considerable TUNEL positive cells were found in the super-early stage; The number of TUNEL positive cells reached peak at 8 to 24 hours in early phase, and then declined ndelayed phase, but was still higher than that in the super-early phase(F=92.34, P < 0.01 ). ②Caspase-3 protein expression: Caspase-3 positive cells were hardly seen in each visual field in the control group; Considerable Caspase-3 positive cells were found in the super-early group; The Caspase-3 positive cells were significantly increased and reached the peak in the early-phase, and then declined almost to the same level in delayed phase compared with the super-early phase (P > 0.05). There was no significant difference in the number of Caspase-3 positive cells between super-early phase group and delayed phase group, but significant difference among the other groups (F =143.23, P < 0.01).

  18. Effects of Total Panax japonicus Saponins on Glial Fibrillary Acidic Protein(GFAP) and Growth Associated Protein 43(GAP 43) in Chronic Cerebral Ischemia Rats%竹节参总皂苷对慢性脑缺血大鼠海马GFAP、GAP-43表达的影响

    Institute of Scientific and Technical Information of China (English)

    王敏; 张秋霞; 邹海艳; 赵晖; 李佳

    2013-01-01

    Objective: To observe the effect of total rhizoma panacis japonica saponins( Trpjs ) on the expression of glial fibrillary acidic protein ( GFAP ) and growth-associated protein ( GAP-43 ) in hippocampus of chronic cerebral ischemia rats. Methods: The chronic cerebral ischemia model rats were established by ligation of bilateral cephalic artery. Expressions of GFAP and GAP-43 protein in hippocampus region were measured by immune imprinting methods after intragastric administration of Trpjs for 30 days. Results: Expression of GFAP protein in hippocampus region increased while expression of GAP-43 protein in hippocampus region decreased obviously in model group. The Trpjs can decrease the expression of GFAP protein in hippocampus region and can increase the expression of GAP-43 protein in hippocampus region significantly ( P <0. 01 ). Conclusion: The Trpjs can inhibit the overreaction of astroglia cell and up-regu-late the expression of GAP-43 protein in hippocampus region in chronic cerebral ischemia rats. This may be one of the mechanisms of improving the capability of learning and memory.%目的:观察竹节参总皂苷(TRPJS)对慢性脑缺血大鼠海马胶质纤维酸性蛋白(GFAP)和神经生长相关蛋白(GAP-43)表达的影响.方法:双侧颈总动脉结扎制备慢性脑缺血大鼠模型,竹节参总皂苷灌胃给药30天后,免疫印迹方法测定海马GFAP和GAP-43的表达.结果:慢性脑缺血大鼠海马GFAP表达增强,GAP-43表达有降低趋势;tRPJS可明显降低GFAP表达和增加GAP-43表达(P<0 01).结论:tRPJS可降低慢性脑缺血引起大鼠海马星形胶质细胞过度反应,上调生长相关蛋白GAP-43,这可能是其提高学习记忆的作用机制.

  19. Neuro-glial crosstalk in inflammatory bowel disease.

    OpenAIRE

    Neunlist, Michel; Van Landeghem, Lien; Bourreille, Arnaud; Savidge, T.

    2008-01-01

    Inflammatory bowel disease (IBD) is a multifactorial disease in which environmental, immune and genetic factors are involved in the pathogenesis. Although biological therapies (antibodies anti-tumour necrosis factor-alpha or anti-integrin) have considerably improved the symptoms and quality of life of IBD patients, some drawbacks have emerged limiting their long-term use. In addition, prevention of relapses and treatment of resistant ulcers remains a clinical challenge. In this context, a bet...

  20. 40 CFR 79.67 - Glial fibrillary acidic protein assay.

    Science.gov (United States)

    2010-07-01

    ... addition to information meeting the requirements stated under 40 CFR 79.60, the following specific... use rocking or orbital shakers. Perform the following steps in enough solution to cover the nitrocellulose sheets to a depth of 1 cm. (A) Incubate 20 minutes in fixer (25 percent (v/v) isopropanol,...