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Sample records for differentiation postnatal myelination

  1. Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor

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    Abi Ghanem, Charly; Degerny, Cindy; Hussain, Rashad; Liere, Philippe; Pianos, Antoine; Tourpin, Sophie; Habert, René; Schumacher, Michael

    2017-01-01

    The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis. PMID:29107990

  2. Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development.

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    Ibarrola, N; Rodríguez-Peña, A

    1997-03-28

    To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.

  3. Postnatal development of EEG patterns, catecholamine contents and myelination, and effect of hyperthyroidism in Suncus brain.

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    Takeuchi, T; Sitizyo, K; Harada, E

    1998-03-01

    The postnatal development of the central nervous system (CNS) in house musk shrew in the early stage of maturation was studied. The electroencephalogram (EEG) and visual evoked potential (VEP) in association with catecholamine contents and myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the 20th day of postnatal age. Different EEG patterns which were specific to behavioral states (awake and drowsy) were first recorded on the 5th day, and the total power which was obtained by power spectrum analysis increased after this stage. The latencies of all peaks in VEP markedly shortened between the 5th and the 7th day. Noradrenalin (NA) content of the brain showed a slight increase after the 3rd day, and reached maximum levels on the 7th day, which was delayed a few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon occurred from the 7th to the 10th day. These morphological changes in the brain advanced at the identical time-course to those in the electrophysiological development and increment of DA and NA contents.

  4. Postnatal Sonic hedgehog (Shh) responsive cells give rise to oligodendrocyte lineage cells during myelination and in adulthood contribute to remyelination.

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    Sanchez, Maria A; Armstrong, Regina C

    2018-01-01

    Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive myelination during postnatal development. During this postnatal period of oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to examine their contribution to the regenerative response during remyelination. Bitransgenic mouse lines were generated for induced genetic fate-labeling of cells actively transcribing Shh or Gli1. Gli1 transcription is an effective readout for canonical Shh signaling. Shh CreERT2 mice and Gli1 CreERT2 mice were crossed to either R26 tdTomato mice to label cells with red fluorescence, or, R26 IAP mice to label membranes with alkaline phosphatase. When tamoxifen (TMX) was given on postnatal days 6-9 (P6-9), Shh ligand synthesis was prevalent in neurons of Shh CreERT2 ; R26 tdTomato mice and Shh CreERT2 ;R26 IAP mice. In Gli1 CreERT2 crosses, TMX from P6-9 detected Gli1 transcription in cells that populated the corpus callosum (CC) during postnatal myelination. Delaying TMX to P14-17, after the peak of oligodendrogenesis, significantly reduced labeling of Shh synthesizing neurons and Gli1 expressing cells in the CC. Importantly, Gli1 CreERT2 ;R26 tdTomato mice given TMX from P6-9 showed Gli1 fate-labeled cells in the adult (P56) CC, including cycling progenitor cells identified by EdU incorporation and NG2 immunolabeling. Furthermore, after cuprizone demyelination of the adult CC, Gli1 fate-labeled cells incorporated EdU and were immunolabeled by NG2 early during remyelination while forming myelin-like membranes after longer periods for remyelination to progress. These studies reveal a postnatal cell population with transient Shh signaling that contributes to oligodendrogenesis during CC myelination, and gives rise to cells that continue to proliferate in adulthood and contribute to CC remyelination. Published by Elsevier Inc.

  5. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

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    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

  6. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

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    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  7. Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease

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    Abhilash P. Appu

    2017-06-01

    Full Text Available Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA, a deacetylase that catabolizes N-acetylaspartate (NAA. The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease. We evaluated various serological parameters, oxidative stress, inflammatory and neurodegeneration markers and the results showed that there were no pathological alterations in any measure with increased brain NAA levels. We examined oxidative stress markers, malondialdehyde content (indicator of lipid peroxidation, expression of NADPH oxidase and nuclear translocation of the stress-responsive transcription factor nuclear factor (erythroid-derived 2-like 2 (NRF-2 in brain. We also examined additional pathological markers by immunohistochemistry and the expression of activated caspase-3 and interleukin-6 by Western blot. None of the markers were increased in the brains of M-NAA treated mice, and no vacuoles were observed in any brain region. These results show that ASPA expression prevents the pathologies associated with excessive NAA concentrations in the brain during postnatal myelination. We hypothesize that the pathogenesis of Canavan disease involves not only disrupted NAA metabolism, but also excessive NAA related signaling processes in oligodendrocytes that have not been fully determined and we discuss some of the potential mechanisms.

  8. Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism-like behavior in a rat model of diffuse white matter injury.

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    van Tilborg, Erik; Achterberg, E J Marijke; van Kammen, Caren M; van der Toorn, Annette; Groenendaal, Floris; Dijkhuizen, Rick M; Heijnen, Cobi J; Vanderschuren, Louk J M J; Benders, Manon N J L; Nijboer, Cora H A

    2018-01-01

    Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism-spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets. In the present study, we developed a multiple-hit animal model of diffuse WMI by combining fetal inflammation and postnatal hypoxia in rats. We characterized the effects on white matter development and functional outcome by immunohistochemistry, MRI and behavioral paradigms. Combined fetal inflammation and postnatal hypoxia resulted in delayed cortical myelination, microglia activation and astrogliosis at P18, together with long-term changes in oligodendrocyte maturation as observed in 10 week old animals. Furthermore, rats with WMI showed impaired motor performance, increased anxiety and signs of autism-like behavior, i.e. reduced social play behavior and increased repetitive grooming. In conclusion, the combination of fetal inflammation and postnatal hypoxia in rats induces a pattern of brain injury and functional impairments that closely resembles the clinical situation of diffuse WMI. This animal model provides the opportunity to elucidate pathophysiological mechanisms underlying WMI, and can be used to develop novel treatment options for diffuse WMI in preterm infants. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  9. Cholesterol and myelin biogenesis.

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    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  10. Myelination and myelin disorders

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    Knaap, M.S. van der.

    1991-01-01

    The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1 H and 31 P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs

  11. Magnetic resonance imaging and myelin

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    Adamsbaum, C.; Andre, C.; Rolland, Y.

    1995-01-01

    Postnatal development of the brain is characterized by growth and by myelination. Myelination of the brain normally extends from birth until about two years of age. MRI changes corresponding to the various myelination stages are due mainly to changes in the water content of the cerebral parenchyma. Myelination kinetics follow a fairly precise timetable, with variations across areas of the brain. Abnormalities of white matter are responsible for relatively stereotyped, nonspecific manifestations, which are mainly due to an increase in the amount of water contained in diseased white matter, whatever the cause of the disorder. Interpretation is based on the location, distribution, and progression of lesions. (authors). 7 refs., 5 figs

  12. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve.

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    So Young Jang

    Full Text Available Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination.

  13. Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

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    Gilly Wolf

    2017-06-01

    Full Text Available Bilateral common carotid artery stenosis (BCAS models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month and young adult (3 month female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014: on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049, while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05 compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01 and old control mice (p < 0.05. These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

  14. The rabbit as an animal model for post-natal vitreous matrix differentiation and degeneration

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    Los, L. I.

    2008-01-01

    Purpose This study evaluates whether rabbits are a suitable animal model to study post-natal vitreous differentiation and degeneration. Methods Human and rabbit eyes of various ages were studied by complementary anatomical techniques, light microscopy, and transmission electron microscopy. Results

  15. Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents.

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    Schild, John H; Kunze, Diana L

    2012-12-24

    Voltage gated ion channels (VGC) make possible the frequency coding of arterial pressure and the neurotransmission of this information along myelinated and unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed in both fiber types, it is the relative expression of each that defines the unique discharge properties of myelinated A-type and unmyelinated C-type baroreceptors. For example, the fast inward Na⁺ current is a major determinant of the action potential threshold and the regenerative transmembrane current needed to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive Na(v)1.7 VGC contributes to the whole cell Na⁺ current. Na(v)1.7 is expressed at a lower density in C-type neurons and in conjunction with TTX-insensitive Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have firing thresholds that are 15-20 mV more negative and upstroke velocities that are 5-10 times faster than unmyelinated C-type neurons. A more depolarized threshold in conjunction with a broader complement of non-inactivating K(V) VGC subtypes produces C-type action potentials that are 3-4 times longer in duration than A-type neurons and at markedly lower levels of cell excitability. Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25% of the total outward K⁺ current. KCa1.1 plays a critically important role in shaping the action potential profile of C-type neurons and strongly impacts neuronal excitability. A-type neurons do not functionally express the KCa1.1 channel despite having a whole cell Ca(V) current quite similar to that of C-type neurons. As a result, A-type neurons do not have the frequency-dependent braking forces of KCa1.1. Lack of a KCa current and only a limited complement of non-inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current that is nearly 10 times larger than in C-type neurons leads to elevated levels of discharge in A-type neurons, a

  16. Differentiation ability of rat postnatal dental pulp cells in vitro.

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    Zhang, W.; Walboomers, X.F.; Wolke, J.G.C.; Bian, Z.; Fan, M.W.; Jansen, J.A.

    2005-01-01

    The current rapid progression in stem cell research has enhanced our knowledge of dental tissue regeneration. In this study, rat dental pulp cells were isolated and their differentiation ability was evaluated. First, dental pulp cells were obtained from maxillary incisors of male Wistar rats.

  17. Cholesterol in myelin biogenesis and hypomyelinating disorders.

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    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

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    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  19. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

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    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-01-01

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture

  20. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

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    Battefeld, A.; Tran, B.T.; Gavrilis, J.; Cooper, E.C.; Kole, Maarten|info:eu-repo/dai/nl/256257574

    2014-01-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav ) channels in the axonal

  1. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

    NARCIS (Netherlands)

    Battefeld, A.; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-01-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the

  2. Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system.

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    Potzner, Michaela R; Griffel, Carola; Lütjen-Drecoll, Elke; Bösl, Michael R; Wegner, Michael; Sock, Elisabeth

    2007-08-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5' flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation.

  3. Prolonged Sox4 Expression in Oligodendrocytes Interferes with Normal Myelination in the Central Nervous System▿ †

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    Potzner, Michaela R.; Griffel, Carola; Lütjen-Drecoll, Elke; Bösl, Michael R.; Wegner, Michael; Sock, Elisabeth

    2007-01-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5′ flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation. PMID:17515609

  4. Ablation of BRaf impairs neuronal differentiation in the postnatal hippocampus and cerebellum.

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    Verena Pfeiffer

    Full Text Available This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12 but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.

  5. Adaptive myelination from fish to man.

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    Baraban, Marion; Mensch, Sigrid; Lyons, David A

    2016-06-15

    Myelinated axons with nodes of Ranvier are an evolutionary elaboration common to essentially all jawed vertebrates. Myelin made by Schwann cells in our peripheral nervous system and oligodendrocytes in our central nervous system has been long known to facilitate rapid energy efficient nerve impulse propagation. However, it is now also clear, particularly in the central nervous system, that myelin is not a simple static insulator but that it is dynamically regulated throughout development and life. New myelin sheaths can be made by newly differentiating oligodendrocytes, and mature myelin sheaths can be stimulated to grow again in the adult. Furthermore, numerous studies in models from fish to man indicate that neuronal activity can affect distinct stages of oligodendrocyte development and the process of myelination itself. This begs questions as to how these effects of activity are mediated at a cellular and molecular level and whether activity-driven adaptive myelination is a feature common to all myelinated axons, or indeed all oligodendrocytes, or is specific to cells or circuits with particular functions. Here we review the recent literature on this topic, elaborate on the key outstanding questions in the field, and look forward to future studies that incorporate investigations in systems from fish to man that will provide further insight into this fundamental aspect of nervous system plasticity. This article is part of a Special Issue entitled SI: Myelin Evolution. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation.

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-07-10

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation*

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-01-01

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. PMID:25998127

  8. Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination.

    Science.gov (United States)

    Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P; Brown, Chester W; John, Gareth R

    2014-06-01

    In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. © 2014. Published by The Company of Biologists Ltd.

  9. Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination

    Science.gov (United States)

    Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

    2014-01-01

    In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

  10. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    Science.gov (United States)

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-05

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

  11. Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate Gyrus of Mice and Rats

    Directory of Open Access Journals (Sweden)

    Tijana Radic

    2017-11-01

    Full Text Available The dentate gyrus (DG is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ. We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX and a marker for mature neurons, calbindin (CB. Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL, indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.

  12. Networks of myelin covariance.

    Science.gov (United States)

    Melie-Garcia, Lester; Slater, David; Ruef, Anne; Sanabria-Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2018-04-01

    Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, ). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these "networks of myelin covariance" (Myelin-Nets). The Myelin-Nets were built from quantitative Magnetization Transfer data-an in-vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin-Nets. We therefore selected two age groups: Young-Age (20-31 years old) and Old-Age (60-71 years old) and a pool of participants from 48 to 87 years old for a Myelin-Nets aging trajectory study. We found that the topological organization of the Myelin-Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin-Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  13. Localization of c-MYB in differentiated cells during postnatal molar and alveolar bone development

    Czech Academy of Sciences Publication Activity Database

    Lungová, Vlasta; Buchtová, Marcela; Janečková, Eva; Tucker, A.S.; Knopfová, L.; Šmarda, J.; Matalová, Eva

    2012-01-01

    Roč. 120, č. 6 (2012), 495-504 ISSN 0909-8836 R&D Projects: GA ČR GCP302/12/J059 Institutional research plan: CEZ:AV0Z50450515 Keywords : c-myb * tooth * postnatal Subject RIV: FF - HEENT, Dentistry Impact factor: 1.420, year: 2012

  14. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

    Science.gov (United States)

    Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

    2017-01-16

    Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: Peffect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

  15. Heteromeric K(v)7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

    NARCIS (Netherlands)

    Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.; Kole, Maarten H. P.

    2014-01-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na-v) channels in the

  16. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  17. Networks of myelin covariance

    Science.gov (United States)

    Slater, David; Ruef, Anne; Sanabria‐Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2017-01-01

    Abstract Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, 2013). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these “networks of myelin covariance” (Myelin‐Nets). The Myelin‐Nets were built from quantitative Magnetization Transfer data—an in‐vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin‐Nets. We therefore selected two age groups: Young‐Age (20–31 years old) and Old‐Age (60–71 years old) and a pool of participants from 48 to 87 years old for a Myelin‐Nets aging trajectory study. We found that the topological organization of the Myelin‐Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin‐Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. PMID:29271053

  18. Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.

    Science.gov (United States)

    Piao, Jinying; Tsuji, Kunikazu; Ochi, Hiroki; Iwata, Munetaka; Koga, Daisuke; Okawa, Atsushi; Morita, Sadao; Takeda, Shu; Asou, Yoshinori

    2013-10-23

    Sirtuin 6 (Sirt6) is a mammalian homologue of NAD⁺-dependent histone deacetylase Sir2. Although Sirt6⁻/⁻ mice exhibit growth retardation, the role of Sirt6 in cartilage metabolism is unclear. The aim of this study was to investigate the Sirt6 signaling pathway in cartilage metabolism. Immunohistological evaluation of the tibial growth plate in Sirt6⁻/⁻ mice exhibited impaired proliferation and differentiation of chondrocytes, reduced expression of Indian hedgehog (Ihh), and a senescent phenotype. When Sirt6 was knocked down in chondrocytes in vitro, expression of Ihh and its downstream genes were reduced. Impaired differentiation by Sirt6 silencing was completely rescued by administration of a Hh signal agonist. When sirtuins were activated, chondrocyte differentiation was enhanced together with activation of Ihh signal, and these effects were abrogated by Sirt6 silencing. ChIP assay revealed the affinity of ATF4 to the Ihh promoter was markedly decreased by Sirt6 knockdown. These data indicate Sirt6 directly controls proliferation and differentiation of chondrocytes.

  19. Evaluation of myelination and myelination disorders with turbo inversion recovery magnetic resonance imaging

    International Nuclear Information System (INIS)

    Daldrup, H.E.; Schuierer, G.; Link, T.M.; Moeller, H.; Bick, U.; Peters, P.E.; Kurlemann, G.

    1997-01-01

    The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p < 0.05). Forty-two neurologically abnormal patients displayed a normal myelination on all sequences, whereas 23 showed an abnormal myelination. The TIRSE sequence provided a sensitive and specific depiction of an abnormal myelination in all of these patients. The TIRSE sequence provided additional information to conventional pulse sequences in determining myelination disorders in children, especially in children older than 2 years. (orig.)

  20. PRENATAL HYPOXIA IN DIFFERENT PERIODS OF EMBRYOGENESIS DIFFERENTIALLY AFFECTS CELL MIGRATION, NEURONAL PLASTICITY AND RAT BEHAVIOR IN POSTNATAL ONTOGENESIS

    Directory of Open Access Journals (Sweden)

    Dmitrii S Vasilev

    2016-03-01

    Full Text Available Long-term effects of prenatal hypoxia on embryonic days E14 or E18 on the number, type and localization of cortical neurons, density of labile synaptopodin-positive dendritic spines and parietal cortex-dependent behavioral tasks were examined in the postnatal ontogenesis of rats. An injection of 5’ethynyl-2’deoxyuridine to pregnant rats was used to label neurons generated on E14 or E18 in the fetuses. In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III. It was shown that hypoxia both on E14 and E18 results in disruption of neuroblast generation and migration but affects different cell populations. In rat pups subjected to hypoxia on E14, the total number of labeled cells in the parietal cortex was decreased while the number of labeled neurons scattered within the superficial cortical layers was increased. In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers. It can be suggested that prenatal hypoxia both on E14 and E18 causes a disruption in neuroblast migration but with a different outcome. Only in rats subjected to hypoxia on E14 did we observe a reduction in the total number of pyramidal cortical neurons and the density of labile synaptopodin-positive dendritic spines in the molecular cortical layer during the first month after birth which affected development of the cortical functions. As a result, rats subjected to hypoxia on E14, but not on E18, had impaired development of the whisker-placing reaction and reduced ability to learn reaching by a forepaw. The data obtained suggest that hypoxia on E14 in the period of generation of the cells, which later differentiate into the pyramidal cortical neurons of the V-VI layers and form cortical minicolumns

  1. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  2. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.

    Science.gov (United States)

    Hendrickx, Debbie A E; Schuurman, Karianne G; van Draanen, Michael; Hamann, Jörg; Huitinga, Inge

    2014-03-31

    The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to

  4. Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production.

    Science.gov (United States)

    Russell, Lauren N; Lampe, Kyle J

    2016-01-01

    Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration. Therefore, researchers have begun exploring combined therapies with biomaterials that promote cell growth and differentiation while localizing cells in the injured area. The regrowth of myelinating oligodendrocytes from neural stem cells through a biomaterials approach may prove to be a beneficial strategy following the onset of demyelination. This article reviews recent advancements in biomaterial strategies for the differentiation of neural stem cells into oligodendrocytes, and presents new data indicating appropriate properties for oligodendrocyte precursor cell growth. In some cases, an increase in oligodendrocyte differentiation alongside neurons is further highlighted for functional improvements where the biomaterial was then tested for increased myelination both in vitro and in vivo. © 2016 S. Karger AG, Basel.

  5. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

    DEFF Research Database (Denmark)

    Gerstenberg, Marina Kjærgaard; Nilsson, C; Secher, A

    2017-01-01

    Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic...... for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling....... assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P

  6. Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord.

    Science.gov (United States)

    Nagashima, K

    1979-12-01

    The anterior funiculus of the spinal cervical cord of post-natal rats was examined ultrastructurally. The myelinating cells found one day after brith contained a large amount of evenly distributed ribosomes up to the outer tongue of mesaxons, representing the cytoplasmic density. These cells were separated by astrocytic processes from the pial basement membrane, even when they were located on the pial surface. Astrocytes contained glial fibrils from one day onwards and often attached their processes to the pial basement membrane. Although the cytoplasmic processes of astrocytes occasionally wrapped axons, they were never shown to form the initial layer of myelin sheaths. However, the tenuous processes of the sub-pial astrocytes were occasionally rolled in myelin lamellae, as if a part of the myelin sheaths was constructed by astrocytic processes. The interpretation for this finding is discussed in relation to function and potency of the astrocytes, and variations and anomalies of nervous ontogeny.

  7. Myelin Basic Protein synthesis is regulated by small non-coding RNA 715

    NARCIS (Netherlands)

    Bauer, N.M.; Moos, C.; van Horssen, J.; Witte, M.E.; van der Valk, P.; Altenhein, B.; Luhmann, H.J.; White, R.

    2012-01-01

    Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP

  8. Differential Effects of Ethanol on c-Jun N-Terminal Kinase, 14-3-3 Proteins, and Bax in Postnatal Day 4 and Postnatal Day 7 Rat Cerebellum

    Science.gov (United States)

    Heaton, Marieta Barrow; Paiva, Michael; Kubovic, Stacey; Kotler, Alexandra; Rogozinski, Jonathan; Swanson, Eric; Madorsky, Vladimir; Posados, Michelle

    2011-01-01

    These studies investigated ethanol effects on upstream cellular elements and interactions which contribute to Bax-related apoptosis in neonatal rat cerebellum at ages of peak ethanol sensitivity (postnatal day 4 [P4]), compared to later ages of relative resistance (P7). Analyses were made of basal levels of the pro-apoptotic c-jun N-termimal kinase (JNK), Bax, and the 14-3-3 anchoring proteins, as well as the responsiveness of these substances to ethanol at P4 versus P7. Dimerization of Bax with 14-3-3 was also investigated at the two ages following ethanol treatment, a process which sequesters Bax in the cytosol, thus inhibiting its mitochondrial translocation and disruption of the mitochondrial membrane potential. Cultured cerebellar granule cells were used to examine the protective potential of JNK inhibition on ethanol-mediated cell death. Basal levels of JNK were significantly higher at P4 than P7, but no differences in the other proteins were found. Activated JNK, and cytosolic and mitochondrially-translocated Bax were increased in P4 but not P7 animals following ethanol exposure, while protective 14-3-3 proteins were increased only at P7. Ethanol treatment resulted in decreases in Bax:14-3-3 heterodimers at P4, but not at P7. Inhibition of JNK activity in vitro provided partial protection against ethanol neurotoxicity. Thus, differential temporal vulnerability to ethanol in this CNS region correlates with differences in both levels of apoptosis-related substances (e.g., JNK), and differential cellular responsiveness, favoring apoptosis at the most sensitive age and survival at the resistant age. The upstream elements contributing to this vulnerability can be targets for future therapeutic strategies. PMID:22169498

  9. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

    Science.gov (United States)

    Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

    2016-01-01

    The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

  10. Adolescent Mouse Takes on An Active Transcriptomic Expression During Postnatal Cerebral Development

    KAUST Repository

    Xu, Wei

    2014-06-01

    Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 (infancy), 59,257,530 (adolescence) and 72,729,636 (adulthood) reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of regulatory genes up-regulated and some crucial pathways activated. Transcription factor (TF) analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regulation. Moreover, our data revealed a drastic increase in myelin basic protein (MBP)-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since mouse adolescence. In addition, differential gene expression analysis indicated the activation of rhythmic pathway, suggesting the function of rhythmic movement since adolescence; Furthermore, during infancy and adolescence periods, gene expression related to axon. repulsion and attraction showed the opposite trends, indicating that axon repulsion was activated after birth, while axon attraction might be activated at the embryonic stage and declined during the postnatal development. Our results from the present study may shed light on the molecular mechanism underlying the postnatal development of the mammalian cerebrum. © 2014 .

  11. Differential expression of secreted phosphoprotein 1 in the motor cortex among primate species and during postnatal development and functional recovery.

    Directory of Open Access Journals (Sweden)

    Tatsuya Yamamoto

    Full Text Available We previously reported that secreted phosphoprotein 1 (SPP1 mRNA is expressed in neurons whose axons form the corticospinal tract (CST of the rhesus macaque, but not in the corresponding neurons of the marmoset and rat. This suggests that SPP1 expression is involved in the functional or structural specialization of highly developed corticospinal systems in certain primate species. To further examine this hypothesis, we evaluated the expression of SPP1 mRNA in the motor cortex from three viewpoints: species differences, postnatal development, and functional/structural changes of the CST after a lesion of the lateral CST (l-CST at the mid-cervical level. The density of SPP1-positive neurons in layer V of the primary motor cortex (M1 was much greater in species with highly developed corticospinal systems (i.e., rhesus macaque, capuchin monkey, and humans than in those with less developed corticospinal systems (i.e., squirrel monkey, marmoset, and rat. SPP1-positive neurons in the macaque monkey M1 increased logarithmically in layer V during postnatal development, following a time course consistent with the increase in conduction velocity of the CST. After an l-CST lesion, SPP1-positive neurons increased in layer V of the ventral premotor cortex, in which compensatory changes in CST function/structure may occur, which positively correlated with the extent of finger dexterity recovery. These results further support the concept that the expression of SPP1 may reflect functional or structural specialization of highly developed corticospinal systems in certain primate species.

  12. Rac1 controls Schwann cell myelination through cAMP and NF2/merlin

    Science.gov (United States)

    Guo, Li; Moon, Chandra; Niehaus, Karen; Zheng, Yi; Ratner, Nancy

    2013-01-01

    During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo, and the shortened processes in cultured Rac1-CKO SCs in vitro. Mechanistically, cyclic adenosine monophosphate (cAMP) levels and E-cadherin expression were decreased in the absence of Rac1, and both were restored by mutation of NF2/merlin. Reduced cAMP is a cause of the myelin deficiency in Rac1-CKO mice, as elevation of cAMP by rolipram in Rac1-CKO mice in vivo allowed myelin formation. Thus NF2/merlin and cAMP function downstream of Rac1 signaling in SC myelination, and cAMP levels control Rac1-regulated SC myelination. PMID:23197717

  13. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

    International Nuclear Information System (INIS)

    Yu, Hui; Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie; Chen, Xin-Lin; Liu, Yong; Gao, Ya

    2016-01-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin"+ cells decreased whilst the percentage of GFAP"+ cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  14. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2016-05-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin{sup +} cells decreased whilst the percentage of GFAP{sup +} cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  15. A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells

    NARCIS (Netherlands)

    Zenker, J.; Stettner, M.; Ruskamo, S.; Domenech-Estevez, E.; Baloui, H.; Medard, J.J.; Verheijen, M.H.G.; Brouwers, J.F.; Kursula, P.; Kieseier, B.C.; Chrast, R.

    2014-01-01

    Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although

  16. A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.

    NARCIS (Netherlands)

    Zenker, Jennifer; ruskamo, salla; domenech-estevez, Enric; medard, jean-jacques; Verheijen, M.H.; Brouwers, Jos|info:eu-repo/dai/nl/173812694; Kursula, Petri; kieseier, bernd; Chrast, Roman

    Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although

  17. Depth-sensing nano-indentation on a myelinated axon at various stages

    International Nuclear Information System (INIS)

    Huang, Wei-Chin; Liao, Jiunn-Der; Lin, Chou-Ching K; Ju, Ming-Shaung

    2011-01-01

    A nano-mechanical characterization of a multi-layered myelin sheath structure, which enfolds an axon and plays a critical role in the transmission of nerve impulses, is conducted. Schwann cells co-cultured in vitro with PC12 cells for various co-culture times are differentiated to form a myelinated axon, which is then observed using a transmission electron microscope. Three major myelination stages, with distinct structural characteristics and thicknesses around the axon, can be produced by varying the co-culture time. A dynamic contact module and continuous depth-sensing nano-indentation are used on the myelinated structure to obtain the load-on-sample versus measured displacement curve of a multi-layered myelin sheath, which is used to determine the work required for the nano-indentation tip to penetrate the myelin sheath. By analyzing the harmonic contact stiffness versus the measured displacement profile, the results can be used to estimate the three stages of the multi-layered structure on a myelinated axon. The method can also be used to evaluate the development stages of myelination or demyelination during nerve regeneration.

  18. Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

    Science.gov (United States)

    Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

    2017-08-15

    The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Antenatal Corticosteroids and Postnatal Fluid Restriction Produce Differential Effects on AQP3 Expression, Water Handling, and Barrier Function in Perinatal Rat Epidermis

    Directory of Open Access Journals (Sweden)

    Johan Agren

    2010-01-01

    Full Text Available Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3 is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18 rat pups were studied after antenatal corticosteroid exposure (ANS, and neonatal (P1 rat pups after an 18 h fast. Transepidermal water loss (TEWL and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration, while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin.

  20. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  1. Ischemic tolerance in pre-myelinated white matter: the role of astrocyte glycogen in brain pathology.

    Science.gov (United States)

    Fern, Robert

    2015-06-01

    In isolated white matter, ischemic tolerance changes dramatically in the period immediately before the onset of myelination. In the absence of an extrinsic energy source, postnatal day 0 to 2 (P0 to P2) white matter axons are here shown to maintain excitability for over twice as long as axons >P2, a differential that was dependent on glycogen metabolism. Prolonged withdrawal of extrinsic energy supply tended to spare axons in zones around astrocytes, which are shown to be the sole repository for glycogen particles in developing white matter. Analysis of mitochondrial volume fraction revealed that neither axons nor astrocytes had a low metabolic rate in neonatal white matter, while oligodendroglia at older ages had an elevated metabolism. The astrocyte population is established early in neural development, and exhibits reduced cell density as maturation progresses and white matter expands. The findings show that this event establishes the necessary conditions for ischemia sensitivity in white matter and indicates that astrocyte proximity may be significant for the survival of neuronal elements in conditions associated with compromised energy supply.

  2. MRI assessment of myelination: an age standardization

    Energy Technology Data Exchange (ETDEWEB)

    Staudt, M. (Kinderklinik Dritter Orden, Passau (Germany)); Schropp, C. (Kinderklinik Dritter Orden, Passau (Germany)); Staudt, F. (Kinderklinik Dritter Orden, Passau (Germany)); Obletter, N. (Radiologische Praxis, Klinikum Ingolstadt (Germany)); Bise, K. (Neuropathologisches Inst., Muenchen Univ. (Germany)); Breit, A. (MR Tomographie, Klinikum Passau (Germany)); Weinmann, H.M. (Kinderklinik Schwabing, Muenchen (Germany))

    1994-04-01

    777 cerebral MRI examinations of children aged 3 days to 14 years were staged for myelination to establish an age standardization. Staging was performed using a system proposed in a previous paper, separately ranking 10 different regions of the brain. Interpretation of the results led to the identification of foue clinical diagnoses that are frequently associated with delays in myelination: West syndrome, cerebral palsy, developmental retardation, and congenital anomalies. In addition, it was found that assessment of myelination in children with head injuries was not practical as alterations in MRI signal can simulate earlier stages of myelination. Age limits were therefore calculated from the case material after excluding all children with these conditions. When simplifications of the definition of the stages are applied, these age limits for the various stages of myelination of each of the 10 regions of the brain make the staging system applicable for routine assessment of myelination. (orig.)

  3. Peripheral myelin protein 22 alters membrane architecture

    Science.gov (United States)

    Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

    2017-01-01

    Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

  4. Ephaptic coupling of myelinated nerve fibers

    DEFF Research Database (Denmark)

    Binczak, S.; Eilbeck, J. C.; Scott, Alwyn C.

    2001-01-01

    Numerical predictions of a simple myelinated nerve fiber model are compared with theoretical results in the continuum and discrete limits, clarifying the nature of the conduction process on an isolated nerve axon. Since myelinated nerve fibers are often arranged in bundles, this model is used...

  5. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

  6. Di-pentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague dawley rat with greater relative potency than other phthalates

    Science.gov (United States)

    Phthalate esters (PEs) constitute a large class of plasticizer compounds that are widely used for many consumer product applications. Ten or more members of the PE class of compounds have been shown to induce male fetal endocrine toxicity and postnatal reproductive malformations ...

  7. Nonenzymatic glycosylation of bovine myelin basic protein

    International Nuclear Information System (INIS)

    Hitz, J.B.

    1987-01-01

    In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with [ 14 C]-galactose and [ 14 C]-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 37 0 C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the [ 14 C]-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using [ 14 C]-glucose and [ 14 C]-mannose with HPLC values at 1/6 and 1/5 of the [ 14 C]-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the [ 3 H]-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general

  8. Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α on phagocytes

    Directory of Open Access Journals (Sweden)

    Reichert Fanny

    2011-03-01

    Full Text Available Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own phagocytosis by simultaneous activation and down-regulation of microglial and macrophage responses. Activation follows myelin binding to receptors that mediate its phagocytosis (e.g. complement receptor-3, which has been previously studied. Down-regulation, which we test here, follows binding of myelin CD47 to the immune inhibitory receptor SIRPα (signal regulatory protein-α on macrophages and microglia. Methods CD47 and SIRPα expression was studied by confocal immunofluorescence microscopy, and myelin phagocytosis by ELISA. Results We first document that myelin, oligodendrocytes and Schwann cells express CD47 without SIRPα and further confirm that microglia and macrophages express both CD47 and SIRPα. Thus, CD47 on myelin can bind to and subsequently activate SIRPα on phagocytes, a prerequisite for CD47/SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis by itself. We then demonstrate that phagocytosis of CD47+/+ myelin is augmented when binding between myelin CD47 and SIRPα on phagocytes is blocked by mAbs against CD47 and SIRPα, indicating that down-regulation of phagocytosis indeed depends on CD47-SIRPα binding. Further, phagocytosis in serum-free medium of CD47+/+ myelin is augmented after knocking down SIRPα levels (SIRPα-KD in phagocytes by lentiviral infection with SIRPα-shRNA, whereas phagocytosis of myelin that lacks CD47 (CD47-/- is not. Thus, myelin CD47 produces SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis in phagocytes

  9. Differential expression and processing of transforming growth factor beta induced protein (TGFBIp) in the normal human cornea during postnatal development and aging

    DEFF Research Database (Denmark)

    Karring, Henrik; Runager, Kasper; Valnickova, Zuzana

    2010-01-01

    Transforming growth factor beta induced protein (TGFBIp, also named keratoepithelin) is an extracellular matrix protein abundant in the cornea. The purpose of this study was to determine the expression and processing of TGFBIp in the normal human cornea during postnatal development and aging...... trimming events from the N-terminus of mature TGFBIp generate TGFBIp isoforms which form a similar "zig-zag" pattern when separated by 2-D polyacrylamide gel electrophoresis (PAGE). This study shows that in humans TGFBIp is more abundant in mature corneas than in the developing cornea...... and that the processing of TGFBIp changes during postnatal development of the cornea. In addition, TGFBIp appears to be degraded in a highly orchestrated manner in the normal human cornea with the resulting C-terminal fragments being retained in the cornea. The age-related changes in the expression and processing...

  10. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuhei Nishimura

    2016-07-01

    Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

  11. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  12. Bony fish myelin: evidence for common major structural glycoproteins in central and peripheral myelin of trout.

    Science.gov (United States)

    Jeserich, G; Waehneldt, T V

    1986-02-01

    Peripheral nervous system (PNS) myelin from the rainbow trout (Salmo gairdneri) banded at a density of 0.38 M sucrose. The main myelin proteins consisted of (1) two basic proteins, BPa and BPb (11,500 and 13,000 MW, similar to those of trout central nervous system (CNS) myelin proteins BP1 and BP2), and (2) two glycosylated components, IPb (24,400 MW) and IPc (26,200 MW). IPc comigrated with trout CNS myelin protein IP2 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas trout CNS myelin protein IP1 had a lower molecular weight (23,000). Following two-dimensional separation, however, both IPb and IPc from PNS showed two components; the more acidic component of IPc comigrated with IP2 from CNS. PNS tissue autolysis led to the formation of IPa (20,000 MW), consisting of two components in isoelectric focusing of which again the more acidic one comigrated with the CNS autolysis product IP0. Limited enzymatic digestion of isolated IP proteins from PNS and CNS led to closely similar degradation patterns, being most pronounced in the case of IP2 and IPc. Immunoblotting revealed that all IP components from trout PNS and CNS myelins reacted with antibodies to trout IP1 (CNS) and bovine P0 protein (PNS) whereas antibodies to rat PLP (CNS) were entirely unreactive. All BP components from trout PNS and CNS myelins bound to antibodies against human myelin basic protein. On the basis of these studies trout PNS and CNS myelins contain at least one common IP glycoprotein, whereas other members of the IP myelin protein family appear closely related. In the CNS myelin of trout the IP components appear to replace PLP.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Phosphorylation of myelin basic proteins and its relevance to myelin biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ulmer, J.B.

    1985-01-01

    Age-related differences in the in vivo incorporation of (32-P) into mouse myelin basic proteins (MBPs) of the central nervous system were observed. The resulting specific radioactivity (S.A.) of the MBPs appeared to be related to the S.A. of the acid-soluble pool of phosphates of myelin. In development, MBPs were phosphorylated in vivo prior to the onset of myelination in the brain, indicating that MBPs are phosphorylated prior to their deposition in the myelin sheath. The incorporation of (32-P) into MBPs and the turnover rates of MBP phosphates were studied in vivo in developmentally-related myelin compartments. The results suggest that there are two separate events in MBP phosphorylation and that the turnover rates of the MBP phosphates derived from these two events are different. A model for MBP phosphorylation, that could explain in these observations, is postulated and discussed in the light of existing information.

  14. Gene profiling of postnatal Mfrprd6 mutant eyes reveals differential accumulation of Prss56, visual cycle and phototransduction mRNAs.

    Directory of Open Access Journals (Sweden)

    Ramani Soundararajan

    Full Text Available Mutations in the membrane frizzled-related protein (MFRP/Mfrp gene, specifically expressed in the retinal pigment epithelium (RPE and ciliary body, cause nanophthalmia or posterior microphthalmia with retinitis pigmentosa in humans, and photoreceptor degeneration in mice. To better understand MFRP function, microarray analysis was performed on eyes of homozygous Mfrprd6 and C57BL/6J mice at postnatal days (P 0 and P14, prior to photoreceptor loss. Data analysis revealed no changes at P0 but significant differences in RPE and retina-specific transcripts at P14, suggesting a postnatal influence of the Mfrprd6 allele. A subset of these transcripts was validated by quantitative real-time PCR (qRT-PCR. In Mfrprd6 eyes, a significant 1.5- to 2.0-fold decrease was observed among transcripts of genes linked to retinal degeneration, including those involved in visual cycle (Rpe65, Lrat, Rgr, phototransduction (Pde6a, Guca1b, Rgs9, and photoreceptor disc morphogenesis (Rpgrip1 and Fscn2. Levels of RPE65 were significantly decreased by 2.0-fold. Transcripts of Prss56, a gene associated with angle-closure glaucoma, posterior microphthalmia and myopia, were increased in Mfrprd6 eyes by 17-fold. Validation by qRT-PCR indicated a 3.5-, 14- and 70-fold accumulation of Prss56 transcripts relative to controls at P7, P14 and P21, respectively. This trend was not observed in other RPE or photoreceptor mutant mouse models with similar disease progression, suggesting that Prss56 upregulation is a specific attribute of the disruption of Mfrp. Prss56 and Glul in situ hybridization directly identified Müller glia in the inner nuclear layer as the cell type expressing Prss56. In summary, the Mfrprd6 allele causes significant postnatal changes in transcript and protein levels in the retina and RPE. The link between Mfrp deficiency and Prss56 up-regulation, together with the genetic association of human MFRP or PRSS56 variants and ocular size, raises the possibility that

  15. Differential effects of developmental hypo- and hyperthyroidism on acetylcholinesterase and butyrylcholinesterase activity in the spinal cord of developing postnatal rat pups.

    Science.gov (United States)

    Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail

    2012-11-01

    The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby

  16. Core binding factor beta (Cbfβ) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation.

    Science.gov (United States)

    Tian, Fei; Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Ma, Junqing; Gao, Bo; Wang, Lin; Li, Yi-Ping; Chen, Wei

    2014-07-01

    Core binding factor beta (Cbfβ) is essential for embryonic bone morphogenesis. Yet the mechanisms by which Cbfβ regulates chondrocyte proliferation and differentiation as well as postnatal cartilage and bone formation remain unclear. Hence, using paired-related homeobox transcription factor 1-Cre (Prx1-Cre) mice, mesenchymal stem cell-specific Cbfβ-deficient (Cbfβ(f/f) Prx1-Cre) mice were generated to study the role of Cbfβ in postnatal cartilage and bone development. These mutant mice survived to adulthood but exhibited severe sternum and limb malformations. Sternum ossification was largely delayed in the Cbfβ(f/f) Prx1-Cre mice and the xiphoid process was noncalcified and enlarged. In newborn and 7-day-old Cbfβ(f/f) Prx1-Cre mice, the resting zone was dramatically elongated, the proliferation zone and hypertrophic zone of the growth plates were drastically shortened and disorganized, and trabecular bone formation was reduced. Moreover, in 1-month-old Cbfβ(f/f) Prx1-Cre mice, the growth plates were severely deformed and trabecular bone was almost absent. In addition, Cbfβ deficiency impaired intramembranous bone formation both in vivo and in vitro. Interestingly, although the expression of Indian hedgehog (Ihh) was largely reduced, the expression of parathyroid hormone-related protein (PTHrP) receptor (PPR) was dramatically increased in the Cbfβ(f/f) Prx1-Cre growth plate, indicating that that Cbfβ deficiency disrupted the Ihh-PTHrP negative regulatory loop. Chromatin immunoprecipitation (ChIP) analysis and promoter luciferase assay demonstrated that the Runx/Cbfβ complex binds putative Runx-binding sites of the Ihh promoter regions, and also the Runx/Cbfβ complex directly upregulates Ihh expression at the transcriptional level. Consistently, the expressions of Ihh target genes, including CyclinD1, Ptc, and Pthlh, were downregulated in Cbfβ-deficient chondrocytes. Taken together, our study reveals not only that Cbfβ is essential for chondrocyte

  17. Differential sensitivity of tachykinin vs. enkephalin gene expression in the posterior striatum in response to acute p-chloroamphetamine treatment during postnatal development.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-01-11

    The acute effects of the monoamine releaser p-chloroamphetamine (pCA, 10 mg/kg, i.p.) on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the anterior (A-STR) vs. posterior (P-STR) striatum were studied in rodents at postnatal days (PND) 10, 21 and 35. Northern analysis 4 h post-injection yielded no significant mRNA changes within the A-STR of any pCA group. However, significant increases (80-200% of saline control) in PPT mRNA levels occurred within the P-STR at all three postnatal ages. Interestingly, pCA did not increase PPE mRNA levels within the P-STR until PND 35 (150% of saline control). Such observation suggests that tachykinin neurons of the P-STR achieve an earlier monoamine-responsive signal transduction linkage to gene regulation as compared to enkephalin neurons. Given its predominance in the caudal regions of the striatum, 5-HT neurotransmission at the 5-HT2 receptor is suggested to play a central role in this mechanism.

  18. Spatiotemporal distribution and function of N-cadherin in postnatal Schwann cells: A matter of adhesion?

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz; Limbach, Christoph

    2010-01-01

    During embryonic development of the peripheral nervous system (PNS), the adhesion molecule neuronal cadherin (N-cadherin) is expressed by Schwann cell precursors and associated with axonal growth cones. N-cadherin expression levels decrease as precursors differentiate into Schwann cells. In this ......During embryonic development of the peripheral nervous system (PNS), the adhesion molecule neuronal cadherin (N-cadherin) is expressed by Schwann cell precursors and associated with axonal growth cones. N-cadherin expression levels decrease as precursors differentiate into Schwann cells....... In this study, we investigated the distribution of N-cadherin in the developing postnatal and adult rat peripheral nervous system. N-cadherin was found primarily in ensheathing glia throughout development, concentrated at neuron-glial or glial-glial contacts of the sciatic nerve, dorsal root ganglia (DRG......), and myenteric plexi. In the sciatic nerve, N-cadherin decreases with age and progress of myelination. In adult animals, N-cadherin was found exclusively in nonmyelinating Schwann cells. The distribution of N-cadherin in developing E17 DRG primary cultures is similar to what was observed in vivo. Functional...

  19. Astrocytes promote myelination in response to electrical impulses.

    Science.gov (United States)

    Ishibashi, Tomoko; Dakin, Kelly A; Stevens, Beth; Lee, Philip R; Kozlov, Serguei V; Stewart, Colin L; Fields, R Douglas

    2006-03-16

    Myelin, the insulating layers of membrane wrapped around axons by oligodendrocytes, is essential for normal impulse conduction. It forms during late stages of fetal development but continues into early adult life. Myelination correlates with cognitive development and can be regulated by impulse activity through unknown molecular mechanisms. Astrocytes do not form myelin, but these nonneuronal cells can promote myelination in ways that are not understood. Here, we identify a link between myelination, astrocytes, and electrical impulse activity in axons that is mediated by the cytokine leukemia inhibitory factor (LIF). These findings show that LIF is released by astrocytes in response to ATP liberated from axons firing action potentials, and LIF promotes myelination by mature oligodendrocytes. This activity-dependent mechanism promoting myelination could regulate myelination according to functional activity or environmental experience and may offer new approaches to treating demyelinating diseases.

  20. Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep

    DEFF Research Database (Denmark)

    Khanal, Prabhat; Axel, Anne Marie Dixen; Kongsted, Anna Hauntoft

    2015-01-01

    AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were......) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. RESULTS......: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than...

  1. Late gestation over- and undernutrition predispose for visceral adiposity in response to a post-natal obesogenic diet, but with differential impacts on glucose-insulin adaptations during fasting in lambs

    DEFF Research Database (Denmark)

    Khanal, Prabhat; Husted, Sanne Vinter; Axel, Anne Marie Dixen

    2014-01-01

    -fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. Results: Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting......, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. Conclusion: Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability...... of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life. © 2013 Scandinavian Physiological Society....

  2. Myelin basic protein in brains of rats with low dose lead encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sundstroem, R; Karlsson, B

    1987-02-01

    In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1-15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation. The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15-200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.

  3. Remarkable Stability of Myelinating Oligodendrocytes in Mice

    Directory of Open Access Journals (Sweden)

    Richa B. Tripathi

    2017-10-01

    Full Text Available New myelin-forming oligodendrocytes (OLs are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover. To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months and motor cortex (∼70% survival than in corticospinal tract or optic nerve (50%–60% survival. Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year.

  4. Myelination competent conditionally immortalized mouse Schwann cells

    NARCIS (Netherlands)

    Saavedra, José T.; Wolterman, Ruud A.; Baas, Frank; ten Asbroek, Anneloor L. M. A.

    2008-01-01

    Numerous mouse myelin mutants are available to analyze the biology of the peripheral nervous system related to health and disease in vivo. However, robust in vitro biochemical characterizations of players in peripheral nerve processes are still not possible due to the limited growth capacities of

  5. Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

    Science.gov (United States)

    Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

    2017-06-01

    Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

  6. Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.

    Directory of Open Access Journals (Sweden)

    Charles F Babbs

    Full Text Available This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity.

  7. High cholesterol level is essential for myelin membrane growth.

    Science.gov (United States)

    Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

    2005-04-01

    Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

  8. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  9. Myelination progression in language-correlated regions in brain of normal children determined by quantitative MRI assessment.

    Science.gov (United States)

    Su, Peijen; Kuan, Chen-Chieh; Kaga, Kimitaka; Sano, Masaki; Mima, Kazuo

    2008-12-01

    To investigate the myelination progression course in language-correlated regions of children with normal brain development by quantitative magnetic resonance imaging (MRI) analysis compared with histological studies. The subjects were 241 neurologically intact neonates, infants and young children (128 boys and 113 girls) who underwent MRI between 2001 and 2007 at the University of Tokyo Hospital, ranging in age from 0 to 429 weeks corrected by postnatal age. To compare their data with adult values, 25 adolescents and adults (14 men and 11 women, aged from 14 to 83 years) were examined as controls. Axial T2-weighted images were obtained using spin-echo sequences at 1.5 T. Subjects with a history of prematurity, birth asphyxia, low Apgar score, seizures, active systemic disease, congenital anomaly, delayed development, infarcts, hemorrhages, brain lesions, or central nervous system malformation were excluded from the analysis. Seven regions of interest in language-correlated areas, namely Broca's area, Wernicke's area, the arcuate fasciculus, and the angular gyrus, as well as their right hemisphere homologous regions, and the auditory cortex, the motor cortex, and the visual cortex were examined. Signal intensity obtained by a region-of-interest methodology progresses from hyper- to hypointensity during myelination. We chose the inferior cerebellar peduncle as the internal standard of maturation. Myelination in all these seven language-correlated regions examined in this study shared the same curve pattern: no myelination was observed at birth, it reached maturation at about 1.5 years of age, and it continued to progress slowly thereafter into adult life. On the basis of scatter plot results, we put these areas into three groups: Group A, which included the motor cortex, the auditory cortex, and the visual cortex, myelinated faster than Group B, which included Broca's area, Wernicke's area, and the angular gyrus before 1.5 years old; Group C, consisting of the

  10. Myelination and isochronicity in neural networks

    Directory of Open Access Journals (Sweden)

    Fumitaka Kimura

    2009-07-01

    Full Text Available Our brain contains a multiplicity of neuronal networks. In many of these, information sent from presynaptic neurons travels through a variety of pathways of different distances, yet arrives at the postsynaptic cells at the same time. Such isochronicity is achieved either by changes in the conduction velocity of axons or by lengthening the axonal path to compensate for fast conduction. To regulate the conduction velocity, a change in the extent of myelination has recently been proposed in thalamocortical and other pathways. This is in addition to a change in the axonal diameter, a previously identified, more accepted mechanism. Thus, myelination is not a simple means of insulation or acceleration of impulse conduction, but it is rather an exquisite way of actively regulating the timing of communication among various neuronal connections with different length.

  11. Effects of differential postnatal exposure of the rat cerebellum to x-rays on spatial discrimination learning as a function of age and position preference

    International Nuclear Information System (INIS)

    Peters, K.B.

    1979-01-01

    The aim of the present research was to analyze the effects of postnatal exposure of the cerebellum to x-irradiation on the use of proprioceptive feedback in spatial learning. A total of 337 naive male Long-Evans hooded rats were assigned at birth to one of four treatments: 12-15x, 4-5x, 4-15x and control. Subjects assigned to the 12-15x treatment were exposed to 200R at 12 and 13 days of age, and to 150R at 15 days of age. The subjects exposed to the 4-5x schedule received 200R on days 4 and 5. The 4-15x subjects are exposed to 200R on days 4 and 5, and to 150R on days 7, 9, 11, 13, 15. Subjects from each treatment started spatial discrimination testing in a T-shaped water maze at 30 to 31, 60 to 63, or 180 to 185 days of age. A preference effect was evident in the control, 12-15x and 4-5x subjects, but not in the 4-15x subjects during acquisition testing. Those control, 12-15x and 4-5x subjects trained against their preference made more errors and required more trials to attain acquisition criterion than did those subjects trained toward their preference. The absence of a position preference in the 4-15x subjects is attributed to the absence of the mossy fiber channel of input to the Purkinje cells in this preparation. Deficits in spatial learning were evident in both the 12-15x and 4-15x subjects, the former differing significantly from control subjects and the latter from the 4-5x subjects in the number of trials needed to complete reversal testing and/or the number of errors made during this phase of the testing. It is the upper portion of the molecular layer, absent in the 12-15x and 4-15x preparations, which receives afferent input from the spinal cord

  12. Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea

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    LaShardai N. Brown

    2017-12-01

    Full Text Available Hearing relies on the transmission of auditory information from sensory hair cells (HCs to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation.

  13. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  14. Myelin injury in the central nervous system and Alzheimer's diseases.

    Science.gov (United States)

    Wang, Sha-Sha; Zhang, Zhao; Zhu, Tian-Bi; Chu, Shi-Feng; He, Wen-Bin; Chen, Nai-Hong

    2018-05-03

    Myelin is a membrane wrapped around the axon of the nerve cell, which is composed of the mature oligodendrocytes. The role of myelin is to insulate and prevent the nerve electrical impulses from the axon of the neurons to the axons of the other neurons, which is essential for the proper functioning of the nervous system. Minor changes in myelin thickness could lead to substantial changes in conduction speed and may thus alter neural circuit function. Demyelination is the myelin damage, which characterized by the loss of nerve sheath and the relative fatigue of the neuronal sheath and axon. Studies have shown that myelin injury may be closely related to neurodegenerative diseases and may be an early diagnostic criteria and therapeutic target. Thus this review summarizes the recent result of pathologic effect and signal pathways of myelin injury in neurodegenerative diseases, especially the Alzheimer's disease to provide new and effective therapeutic targets. Copyright © 2018. Published by Elsevier Inc.

  15. Transverse Magnetic Waves in Myelinated Nerves

    Science.gov (United States)

    2001-10-25

    IN MYELINATED NERVES M. Mª Villapecellín-Cid1, L. Mª Roa2, and J. Reina-Tosina1 1Área de Teoría de la Señal y Comunicaciones , E.S. de Ingeniería...Element Number Author(s) Project Number Task Number Work Unit Number Performing Organization Name(s) and Address(es) Área de Teoría de la Señal...y Comunicaciones , E.S. de Ingeniería, University of Seville, Seville, Spain Performing Organization Report Number Sponsoring/Monitoring Agency Name(s

  16. Fast-spiking Parvalbumin Interneurons are Frequently Myelinated in the Cerebral Cortex of Mice and Humans

    NARCIS (Netherlands)

    Stedehouder, J. (J.); J.J. Couey (Jonathan J); Brizee, D. (D.); B. Hosseini; J.A. Slotman (Johan A.); C.M.F. Dirven (Clemens); G. Shpak (Guy); A.B. Houtsmuller (Adriaan); S.A. Kushner (Steven)

    2017-01-01

    textabstractMyelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination

  17. Disruption of myelination by diagnostic US

    International Nuclear Information System (INIS)

    Ellisman, M.H.; Palmer, D.E.; Andre, M.P.

    1986-01-01

    In order to test for possible effects of US on myelination, the authors exposed 20 unanesthetized rat pups to US intensities consistent with those used for imaging a human fetus in utero. The rats were 3-5 days old and at a stage of myelination similar to that of a human fetus of about 4-5 months. Then animals were exposed for 30 minutes to the beam from a 3.5-MHz transducer (ADR 2130 real-time linear array, SPTA intensity of 0.4 mW/cm/sup 2/ and SATA intensity of 0.05 mW/cm/sup 2/). Control animals were bound and placed in the tank but not exposed for 30 minutes, and taken straight from the cage. Some animals were killed and tissues were processed for electron microscopy immediately after exposure, others were killed after recovery periods of up to 24 hours. Enlargements of the periaxonal space was visible with separation of adjacent paranodal loops and disruption of Schwann cell-axonal junctions in all exposed animals. Paranodal demyelination was also noted in several nodes. Nodes exhibiting this microedematous morphology were apparent even after a 24-hour recovery period but were not found in control preparations

  18. Myelin-associated proteins labelled by slow axonal transport

    International Nuclear Information System (INIS)

    Giorgi, P.P.; DuBois, H.

    1981-01-01

    This paper deals with the problem of protein metabolism and provides evidence that the neuronal contribution to myelin metabolism may be restricted to lipids only. On the other hand this line of research led to the partial characterization of a group of neuronal proteins probably involved in axo-glial interactions subserving the onset of myelination and the structural maintenance of the mature myelin sheath. Intraocular injection of radioactive amino acids allows the study of the anterograde transport of labelled proteins along retinofugal fibres which are well myelinated. Myelin extracted from the optic nerve and tract under these conditions also contains labelled proteins. Three hypotheses are available to explain this phenomenon. To offer an explanation for this phenomenon the work was planned as follows. a) Characterization of the spatio-temporal pattern of labelling of myelin, in order to define the experimental conditions (survival time and region of the optic pathway to be studied) necessary to obtain maximal labelling. b) Characterization (by gel electrophoresis) of the myelin-associated proteins which become labelled by axonal transport, in order to work on a consistent pattern of labelling. c) Investigation of the possible mechanism responsible for the labelling of myelin-associated proteins. (Auth.)

  19. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    NARCIS (Netherlands)

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; de Juan, Virginia Gutiérrez; Jefferies, Harold B. J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona; Woodhoo, Ashwin; Jessen, Kristján R.

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that

  20. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

    Science.gov (United States)

    D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

    2013-04-08

    P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

  1. Salvianolic acid B protects the myelin sheath around injured spinal cord axons

    Directory of Open Access Journals (Sweden)

    Zhe Zhu

    2016-01-01

    Full Text Available Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

  2. Evaluation of dermal myelinated nerve fibers in diabetes mellitus

    Science.gov (United States)

    Peltier, Amanda C.; Myers, M. Iliza; Artibee, Kay J.; Hamilton, Audra D.; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

    2013-01-01

    Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 29–73) underwent skin biopsy of the index finger, nerve conduction studies, and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MC) and their afferent myelinated nerve fibers (p=0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in nerve conduction studies. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN. PMID:23781963

  3. Confocal mapping of myelin figures with micro-Raman spectroscopy

    Science.gov (United States)

    Huang, Jung-Ren; Cheng, Yu-Che; Huang, Hung Ji; Chiang, Hai-Pang

    2018-01-01

    We employ confocal micro-Raman spectroscopy (CMRS) with submicron spatial resolution to study the myelin structures (cylindrical lamellae) composed of nested surfactant C12E3 or lipid DMPC bilayers. The CMRS mapping indicates that for a straight C12E3 myelin, the surfactant concentration increases with the myelin width and is higher in the center region than in the peripheral region. For a curved C12E3 myelin, the convex side has a higher surfactant concentration than the corresponding concave side. The spectrum of DMPC myelins undergoes a qualitative change as the temperature increases above 60 °C, suggesting that the surfactant molecules may be damaged. Our work demonstrates the utility of CMRS in bio-soft material research.

  4. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  5. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    International Nuclear Information System (INIS)

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-01-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  6. Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yun Kyung; Kim, Gunha; Park, Serah; Sim, Ju Hee; Won, You Jin [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hwang, Chang Ho [Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714 (Korea, Republic of); Yoo, Jong Yoon, E-mail: jyyoo@amc.seoul.kr [Department of Rehabilitation Medicine, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hong, Hea Nam, E-mail: hnhong@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

  7. TSC Regulates Oligodendroglial Differentiation and Myelination in the CNS

    Science.gov (United States)

    2011-09-01

    Glutamate-Mediated Apoptosis and Trophic Factor Protection of Immature Oligodendrocytes” Weiss Center for Research, “Death and Survival in the...System, Cold Spring Harbor Laboratories 1994 - 1995 Medical Embryology , PSU/College of Medicine (4 lectures) 1994 – 2000 Molecular...Instructor, Medical Embryology , PSU/College of Medicine (8 lectures) 1997 Biology of Neoplasia (1 lecture) 1999 - 2004 Medical Histology, PSU/College

  8. Localisation of N-acetylaspartate in oligodendrocytes/myelin.

    Science.gov (United States)

    Nordengen, Kaja; Heuser, Christoph; Rinholm, Johanne Egge; Matalon, Reuben; Gundersen, Vidar

    2015-03-01

    The role of N-acetylaspartate in the brain is unclear. Here we used specific antibodies against N-acetylaspartate and immunocytochemistry of carbodiimide-fixed adult rodent brain to show that, besides staining of neuronal cell bodies in the grey matter, N-acetylaspartate labelling was present in oligodendrocytes/myelin in white matter tracts. Immunoelectron microscopy of the rat hippocampus showed that N-acetylaspartate was concentrated in the myelin. Also neuronal cell bodies and axons contained significant amounts of N-acetylaspartate, while synaptic elements and astrocytes were low in N-acetylaspartate. Mitochondria in axons and neuronal cell bodies contained higher levels of N-acetylaspartate compared to the cytosol, compatible with synthesis of N-acetylaspartate in mitochondria. In aspartoacylase knockout mice, in which catabolism of N-acetylaspartate is blocked, the levels of N-acetylaspartate were largely increased in oligodendrocytes/myelin. In these mice, the highest myelin concentration of N-acetylaspartate was found in the cerebellum, a region showing overt dysmyelination. In organotypic cortical slice cultures there was no evidence for N-acetylaspartate-induced myelin toxicity, supporting the notion that myelin damage is induced by the lack of N-acetylaspartate for lipid production. Our findings also implicate that N-acetylaspartate signals on magnetic resonance spectroscopy reflect not only vital neurons but also vital oligodendrocytes/myelin.

  9. Cross-population myelination covariance of human cerebral cortex.

    Science.gov (United States)

    Ma, Zhiwei; Zhang, Nanyin

    2017-09-01

    Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  11. Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study.

    Science.gov (United States)

    Lucia, Federico S; Pacheco-Torres, Jesús; González-Granero, Susana; Canals, Santiago; Obregón, María-Jesús; García-Verdugo, José M; Berbel, Pere

    2018-01-01

    Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC), while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E) 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction delays. These

  12. Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study

    Directory of Open Access Journals (Sweden)

    Federico S. Lucia

    2018-04-01

    Full Text Available Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC, while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI treated rats were studied. One group was MMI-treated from postnatal day (P 0 to P21; some of these rats were also treated with L-thyroxine (T4 from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction

  13. After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

    Science.gov (United States)

    Gomez-Sanchez, Jose A; Pilch, Kjara S; van der Lans, Milou; Fazal, Shaline V; Benito, Cristina; Wagstaff, Laura J; Mirsky, Rhona; Jessen, Kristjan R

    2017-09-13

    There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration. SIGNIFICANCE STATEMENT After injury to peripheral nerves, the myelin and Remak Schwann cells distal to the injury site reorganize and modify their properties to form cells that support the survival of injured neurons, promote axon growth, remove myelin-associated growth inhibitors, and guide regenerating axons to their targets. We show that the

  14. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

    2011-01-01

    of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

  15. Regulation of Central Nervous System Myelination in Higher Brain Functions

    OpenAIRE

    Nickel, Mara; Gu, Chen

    2018-01-01

    The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic sup...

  16. Regulation of Central Nervous System Myelination in Higher Brain Functions

    Directory of Open Access Journals (Sweden)

    Mara Nickel

    2018-01-01

    Full Text Available The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic support and can profoundly affect neural circuit computation. Recent studies have revealed that long-lasting changes of myelination can be induced in these brain regions by experience, such as social isolation, stress, and alcohol abuse, as well as by neurological and psychiatric abnormalities. However, the mechanism and function of these changes remain poorly understood. Myelin regulation represents a new form of neural plasticity. Some progress has been made to provide new mechanistic insights into activity-independent and activity-dependent regulations of myelination in different experimental systems. More extensive investigations are needed in this important but underexplored research field, in order to shed light on how higher brain functions and myelination interplay in the hippocampus and prefrontal cortex.

  17. Rapid myelin water content mapping on clinical MR systems

    International Nuclear Information System (INIS)

    Tonkova, Vyara; Arhelger, Volker; Schenk, Jochen; Neeb, Heiko; Koblenz Univ.

    2012-01-01

    We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T 1 , T * 2 and total water content. Employing the multiexponential T * 2 decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T * 2 curve was compromised to 10 echo times with a T Emax of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T 1 , T * 2 , total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

  18. Vesicular glutamate release from central axons contributes to myelin damage.

    Science.gov (United States)

    Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

    2018-03-12

    The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

  19. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  20. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  1. The experiences of postnatal patients regarding postnatal care in ...

    African Journals Online (AJOL)

    At home they receive care and advice from traditional birth attendants. ... exploratory, descriptive and contextual research method was used in this study. ... relatives when giving health advice on discharge; conflicting postnatal care advice; ...

  2. Activation of MAPK overrides the termination of myelin growth and replaces Nrg1/ErbB3 signals during Schwann cell development and myelination

    NARCIS (Netherlands)

    M.E. Sheean (Maria); E. McShane (Erik); C. Cheret (Cyril); J. Walcher (Jan); T. Müller (Thomas); A. Wulf-Goldenberg (Annika); S. Hoelper (Soraya); A.N. Garratt (Alistair); M. Krüger (Markus); K. Rajewsky (Klaus); D.N. Meijer (Dies); W. Birchmeier (Walter); G.R. Lewin (Gary); M. Selbach (Matthias); C. Birchmeier (Carmen)

    2014-01-01

    textabstractMyelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin

  3. Sustained neonatal hyperthyroidism in the rat affects myelination in the central nervous system.

    Science.gov (United States)

    Marta, C B; Adamo, A M; Soto, E F; Pasquini, J M

    1998-07-15

    We have carried out a study of the effects of sustained neonatal hyperthyroidism on myelin and on the oligodendroglial cells, in an effort to obtain further insight into the molecular mechanisms underlying the action of thyroid hormones on the central nervous system (CNS). Expression of the mRNAs of myelin basic protein (MBP) myelin proteolipid protein (PLP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), transferrin, and c-Jun was investigated in 10- and 17-day-old normal and hyperthyroid rats, using Northern blot analysis. At 10 days of age, the levels of all the explored mRNAs were markedly higher in the experimental animals. The mRNA of transferrin showed a ninefold increase over control values, suggesting the possibility that this putative trophic factor might act as one of the mediators in the action of thyroid hormones. At 17 days of age on the other hand, the levels of all the mRNAs decreased markedly, reaching values below control, except for c-Jun, which remained higher than in normals. At 70 days of age, hyperthyroid rats showed clear evidence of myelin deficit, in agreement with previous results of our laboratories (Pasquini et al.: J Neurochem 57: Suppl S124, 1991). Immunocytochemistry of 70-day-old rat brain tissue sections showed a substantial reduction in the amount of MBP-reacting structures and a marked decrease in the number of oligodendroglial cells. Although the above-mentioned results could be the consequence, as proposed by Barres et al. (Development 120:1097-1108, 1994) and Baas et al. (Glia 19:324-332, 1997) of a premature arrest in oligodendroglial cell proliferation followed by early differentiation, the persistent high levels of expression of c-Jun, together with the dramatic decrease in the number of oligodendrocytes, suggested the possibility that prolonged hyperthyroidism could activate apoptotic mechanisms in the myelin forming cells. Using propidium iodide-labeled isolated oligodendroglial cells, we found, by flow cytometry

  4. Nanoscale Correlated Disorder in Out-of-Equilibrium Myelin Ultrastructure.

    Science.gov (United States)

    Campi, Gaetano; Di Gioacchino, Michael; Poccia, Nicola; Ricci, Alessandro; Burghammer, Manfred; Ciasca, Gabriele; Bianconi, Antonio

    2018-01-23

    Ultrastructural fluctuations at nanoscale are fundamental to assess properties and functionalities of advanced out-of-equilibrium materials. We have taken myelin as a model of supramolecular assembly in out-of-equilibrium living matter. Myelin sheath is a simple stable multilamellar structure of high relevance and impact in biomedicine. Although it is known that myelin has a quasi-crystalline ultrastructure, there is no information on its fluctuations at nanoscale in different states due to limitations of the available standard techniques. To overcome these limitations, we have used scanning micro X-ray diffraction, which is a unique non-invasive probe of both reciprocal and real space to visualize statistical fluctuations of myelin order of the sciatic nerve of Xenopus laevis. The results show that the ultrastructure period of the myelin is stabilized by large anticorrelated fluctuations at nanoscale, between hydrophobic and hydrophilic layers. The ratio between the total thickness of hydrophilic and hydrophobic layers defines the conformational parameter, which describes the different states of myelin. Our key result is that myelin in its out-of-equilibrium functional state fluctuates point-to-point between different conformations showing a correlated disorder described by a Levy distribution. As the system approaches the thermodynamic equilibrium in an aged state, the disorder loses its correlation degree and the structural fluctuation distribution changes to Gaussian. In a denatured state at low pH, it changes to a completely disordered stage. Our results aim to clarify the degradation mechanism in biological systems by associating these states with ultrastructural dynamic fluctuations at nanoscale.

  5. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    Science.gov (United States)

    Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

    2012-01-01

    Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

  6. Rapid myelin water content mapping on clinical MR systems

    Energy Technology Data Exchange (ETDEWEB)

    Tonkova, Vyara; Arhelger, Volker [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Schenk, Jochen [Radiologisches Institut, Koblenz (Germany); Neeb, Heiko [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Koblenz Univ. (Germany). Inst. for Medical Engineering and Information Processing - MTI Mittelrhein

    2012-07-01

    We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T{sub 1}, T{sup *}{sub 2} and total water content. Employing the multiexponential T{sup *}{sub 2} decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T{sup *}{sub 2} curve was compromised to 10 echo times with a T {sub Emax} of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T{sub 1}, T{sup *}{sub 2}, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

  7. Efficient in vivo electroporation of the postnatal rodent forebrain.

    Directory of Open Access Journals (Sweden)

    Camille Boutin

    Full Text Available Functional gene analysis in vivo represents still a major challenge in biomedical research. Here we present a new method for the efficient introduction of nucleic acids into the postnatal mouse forebrain. We show that intraventricular injection of DNA followed by electroporation induces strong expression of transgenes in radial glia, neuronal precursors and neurons of the olfactory system. We present two proof-of-principle experiments to validate our approach. First, we show that expression of a human isoform of the neural cell adhesion molecule (hNCAM-140 in radial glia cells induces their differentiation into cells showing a neural precursor phenotype. Second, we demonstrate that p21 acts as a cell cycle inhibitor for postnatal neural stem cells. This approach will represent an important tool for future studies of postnatal neurogenesis and of neural development in general.

  8. Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

    Science.gov (United States)

    Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

    2018-05-02

    Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

  9. Pengaruh Kekurangan Protein Pre dan Postnatal Terhadap Mineralisasi Gigi

    Directory of Open Access Journals (Sweden)

    Pinandi Sri Pudyani

    2015-11-01

    Full Text Available The accuracy of nutrition quantity during and after pregnancy is needed for supporting division, differentiation and replication of cells during growth stage. Protein is needed to obtain optimally child's body growth and development including tooth. The study was aimed to deteremine the effects of pre and postnatal protein deficiency on tooth mineralization rats model. The study was carried out on 30 Rates norvegicus rats, divided in 3 groups.The first group was fed the protein deficient diet (4% during pre and postnatal period, the second was fed the protein deficient diet (4% only postnatal and the third was fed the postnatal diet. Feeding was carried out until animales aged at 56 days. After that, animals were sacrificed and the width of right mandibular molar prevention layer was histologically analyzed to know the number of tooth mineralization. The result of the study showed significant differences (p<0.05 in width of prevention layer between standard and experimental groups. It's concluded that pre and postnatal protein deficiency were inhibits tooth mineralization.

  10. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

    Institute of Scientific and Technical Information of China (English)

    Yan Zou; De-en Xu; Wei-feng Zhang; Hai-ying Liu; Xia Li; Xing Zhang; Xiao-fang Ma; Yang Sun; Shi-yi Jiang; Quan-hong Ma

    2017-01-01

    The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

  11. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

    Directory of Open Access Journals (Sweden)

    Yan Zou

    2017-01-01

    Full Text Available The contactin-associated protein (Caspr family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1, CNTNAP2 (Caspr2, CNTNAP3 (Caspr3, CNTNAP4 (Caspr4 and CNTNAP5 (Caspr5, Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

  12. A Novel Approach for Studying the Physiology and Pathophysiology of Myelinated and Non-Myelinated Axons in the CNS White Matter.

    Directory of Open Access Journals (Sweden)

    Lijun Li

    Full Text Available Advances in brain connectomics set the need for detailed knowledge of functional properties of myelinated and non-myelinated (if present axons in specific white matter pathways. The corpus callosum (CC, a major white matter structure interconnecting brain hemispheres, is extensively used for studying CNS axonal function. Unlike another widely used CNS white matter preparation, the optic nerve where all axons are myelinated, the CC contains also a large population of non-myelinated axons, making it particularly useful for studying both types of axons. Electrophysiological studies of optic nerve use suction electrodes on nerve ends to stimulate and record compound action potentials (CAPs that adequately represent its axonal population, whereas CC studies use microelectrodes (MEs, recording from a limited area within the CC. Here we introduce a novel robust isolated "whole" CC preparation comparable to optic nerve. Unlike ME recordings where the CC CAP peaks representing myelinated and non-myelinated axons vary broadly in size, "whole" CC CAPs show stable reproducible ratios of these two main peaks, and also reveal a third peak, suggesting a distinct group of smaller caliber non-myelinated axons. We provide detailed characterization of "whole" CC CAPs and conduction velocities of myelinated and non-myelinated axons along the rostro-caudal axis of CC body and show advantages of this preparation for comparing axonal function in wild type and dysmyelinated shiverer mice, studying the effects of temperature dependence, bath-applied drugs and ischemia modeled by oxygen-glucose deprivation. Due to the isolation from gray matter, our approach allows for studying CC axonal function without possible "contamination" by reverberating signals from gray matter. Our analysis of "whole" CC CAPs revealed higher complexity of myelinated and non-myelinated axonal populations, not noticed earlier. This preparation may have a broad range of applications as a robust

  13. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    OpenAIRE

    Daisuke Ino; Hiroshi Sagara; Junji Suzuki; Kazunori Kanemaru; Yohei Okubo; Masamitsu Iino

    2015-01-01

    Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulati...

  14. A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments

    OpenAIRE

    Court, Felipe A.; Hewitt, Jane E.; Davies, Kay; Patton, Bruce L.; Uncini, Antonino; Wrabetz, Lawrence; Feltri, M. Laura

    2009-01-01

    Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramon-y-Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot-Marie-Tooth 4F. Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (internodes) and reduce...

  15. Between postnationality and postcoloniality

    DEFF Research Database (Denmark)

    Zhang, Chenchen

    2014-01-01

    , both as normative expectations and institutional construction, and the post/neocolonial condition as expressed in the politics of citizenship and migration in today’s Europe. I argue that the exclusion and exploitation of postcolonial migrants have both underpinned and betrayed the EU’s ambition to re......-establish Europe as a leading ‘normative power’ committed to the value of human rights. When shifting the focus from EU citizenship and its reproduction of differential inclusion and essentialist cultural identity to migrant subjectivity, the paper engages with the emerging field of critical citizenship studies...

  16. Diffusion-weighted MRI of myelination in the rat brain following treatment with gonadal hormones

    International Nuclear Information System (INIS)

    Prayer, D.; Roberts, T.; Barkovich, A.J.; Prayer, L.; Kucharczyk, J.; Moseley, M.; Arieff, A.

    1997-01-01

    Previous studies have demonstrated the ability of high-resolution diffusion-weighted MRI to show maturation of white-matter structures in the developing rat brain. The purpose of this study was to investigate the influence of gonadal steroid hormones on the rate of this development. Starting from their second postnatal day, 16 rat-pups of either sex were repeatedly treated with subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17 dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and hemisphere commissures was assessed. Diffusion-weighted images were processed to produce ''anisotropy index maps'', previously shown to be sensitive to white-matter maturation. Compared with untreated rat-pups, estrogen-treated animals showed accelerated, and testosterone-treated animals delayed maturation on anisotropy index maps and histological sections. In all animals, maturational changes appeared earlie on anisotropy index maps than on other MRI sequences or on myelin-sensitive stained sections. Diffusion-weighted imaging, and the construction of spatial maps sensitive to diffusion anisotropy, seem to be the most sensitive approach for the detection of maturational white-matter changes, and thus may hold potential for early diagnosis of temporary delay or permanent disturbances of white-matter development. (orig.). With 6 figs., 1 tab

  17. Diffusion-weighted MRI of myelination in the rat brain following treatment with gonadal hormones

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, D. [Department of Radiology, Section of Neuroradiology, University of Vienna (Austria); Roberts, T. [Department of Radiology, Section of Neuroradiology, University of California at San Francisco (UCSF), CA (United States); Barkovich, A.J. [Department of Radiology, Section of Neuroradiology, University of California at San Francisco (UCSF), CA (United States); Prayer, L. [Department of Radiology, Section of Neuroradiology, University of Vienna (Austria); Kucharczyk, J. [Department of Radiology, Section of Neuroradiology, University of California at San Francisco (UCSF), CA (United States); Moseley, M. [Department of Radiology, Section of Neuroradiology, University of California at San Francisco (UCSF), CA (United States); Arieff, A. [Department of Medicine, Geriatrics Section, Veteran`s Affairs Medical Center and University of California at San Francisco (UCSF), CA (United States)

    1997-05-01

    Previous studies have demonstrated the ability of high-resolution diffusion-weighted MRI to show maturation of white-matter structures in the developing rat brain. The purpose of this study was to investigate the influence of gonadal steroid hormones on the rate of this development. Starting from their second postnatal day, 16 rat-pups of either sex were repeatedly treated with subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17 dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and hemisphere commissures was assessed. Diffusion-weighted images were processed to produce ``anisotropy index maps``, previously shown to be sensitive to white-matter maturation. Compared with untreated rat-pups, estrogen-treated animals showed accelerated, and testosterone-treated animals delayed maturation on anisotropy index maps and histological sections. In all animals, maturational changes appeared earlie on anisotropy index maps than on other MRI sequences or on myelin-sensitive stained sections. Diffusion-weighted imaging, and the construction of spatial maps sensitive to diffusion anisotropy, seem to be the most sensitive approach for the detection of maturational white-matter changes, and thus may hold potential for early diagnosis of temporary delay or permanent disturbances of white-matter development. (orig.). With 6 figs., 1 tab.

  18. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Johann eSteiner

    2014-11-01

    Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  19. The effect of DDT and dieldrin on myelinated nerve fibres

    NARCIS (Netherlands)

    Bercken, J. van den

    1972-01-01

    The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be

  20. The deterioration seen in myelin related morphophysiology in ...

    African Journals Online (AJOL)

    Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental ...

  1. Neuroimaging evidence of deficient axon myelination in Wolfram syndrome.

    Science.gov (United States)

    Lugar, Heather M; Koller, Jonathan M; Rutlin, Jerrel; Marshall, Bess A; Kanekura, Kohsuke; Urano, Fumihiko; Bischoff, Allison N; Shimony, Joshua S; Hershey, Tamara

    2016-02-18

    Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.

  2. Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

    NARCIS (Netherlands)

    Hendrickx, D.A.E.

    2018-01-01

    Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

  3. Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats.

    Science.gov (United States)

    Andrews, Jessica L; Newell, Kelly A; Matosin, Natalie; Huang, Xu-Feng; Fernandez-Enright, Francesca

    2015-12-03

    Postnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n=6/group) were sacrificed at PN12, 5weeks, or 14weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5weeks (p>0.05). At 14weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014≤p≤0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that

  4. Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.

    Science.gov (United States)

    Matthews, Paul R; Eastwood, Sharon L; Harrison, Paul J

    2012-01-01

    Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology.

  5. Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair.

    Science.gov (United States)

    Kim, Han-Seop; Lee, Jungwoon; Lee, Da Yong; Kim, Young-Dae; Kim, Jae Yun; Lim, Hyung Jin; Lim, Sungmin; Cho, Yee Sook

    2017-06-06

    Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Maksimov, G. V.; Mosekilde, Erik

    2011-01-01

    . Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes...... in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from...

  7. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

    International Nuclear Information System (INIS)

    Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

    2009-01-01

    Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase α, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET 2 ) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate

  8. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

    Directory of Open Access Journals (Sweden)

    Pujiao Yu

    2016-01-01

    Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

  9. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Denninger, Andrew R. [Boston College, Chestnut Hill, MA 02467 (United States); Demé, Bruno; Cristiglio, Viviana [Institut Laue–Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9 (France); LeDuc, Géraldine [European Synchrotron Radiation Facility (ESRF), CS 40220, F-38043 Grenoble CEDEX 9 (France); Feller, W. Bruce [NOVA Scientific Inc., Sturbridge, MA 01566 (United States); Kirschner, Daniel A., E-mail: kirschnd@bc.edu [Boston College, Chestnut Hill, MA 02467 (United States)

    2014-12-01

    The structure of internodal myelin in the rodent central and peripheral nervous systems has been determined using neutron diffraction. The kinetics of water exchange in these tissues is also described. Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.

  10. Formation of compact myelin is required for maturation of the axonal cytoskeleton

    Science.gov (United States)

    Brady, S. T.; Witt, A. S.; Kirkpatrick, L. L.; de Waegh, S. M.; Readhead, C.; Tu, P. H.; Lee, V. M.

    1999-01-01

    Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

  11. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

    International Nuclear Information System (INIS)

    Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

  12. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    Directory of Open Access Journals (Sweden)

    Daisuke Ino

    2015-09-01

    Full Text Available Schwann cells (SCs myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca2+ increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.

  13. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...

  14. Regulation of myelin genes implicated in psychiatric disorders by functional activity in axons

    Directory of Open Access Journals (Sweden)

    Philip R Lee

    2009-06-01

    Full Text Available Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons.

  15. Variation in myelin lipid composition induced by change in environmental temperature of goldfish (Carassius auratus L. )

    Energy Technology Data Exchange (ETDEWEB)

    Selivonchick, D.P.; Roots, B.I.

    1976-04-01

    Goldfish (Carassius auratus L.) were acclimated to 5, 15, and 30/sup 0/C, and the lipid and protein composition of brain and spinal cord myelin was determined. Goldfish myelin contains less galactolipid, but more protein and phospholipid than mammalian and bird myelin. Phosphatidyl choline was the predominant phospholipid in both brain and spinal cord myelin. Fish myelin also showed a greater plasmalogen content with an average ethanolamine plasmalogen/total phosphatidyl ethanolamine ratio of 0.84. Total brain and myelin lipids, with the exception of plasmalogens, showed a resistance to change with thermal acclimation. Differences between brain and spinal cord myelin protein and phospholipids were not observed. It is suggested that temperature acclimation in poikilotherms may be used as a tool in the study of membrane adaptability.

  16. Investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and myelin repair.

    Directory of Open Access Journals (Sweden)

    Jennifer K Sabo

    Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin

  17. Activation of postnatal neural stem cells requires nuclear receptor TLX.

    Science.gov (United States)

    Niu, Wenze; Zou, Yuhua; Shen, Chengcheng; Zhang, Chun-Li

    2011-09-28

    Neural stem cells (NSCs) continually produce new neurons in postnatal brains. However, the majority of these cells stay in a nondividing, inactive state. The molecular mechanism that is required for these cells to enter proliferation still remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls the activation status of postnatal NSCs in mice. Lineage tracing indicates that TLX-expressing cells give rise to both activated and inactive postnatal NSCs. Surprisingly, loss of TLX function does not result in spontaneous glial differentiation, but rather leads to a precipitous age-dependent increase of inactive cells with marker expression and radial morphology for NSCs. These inactive cells are mispositioned throughout the granular cell layer of the dentate gyrus during development and can proliferate again after reintroduction of ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global expression signature, which includes the p53 signaling pathway. TLX regulates p21 expression in a p53-dependent manner, and acute removal of p53 can rescue the proliferation defect of TLX-null NSCs in culture. Together, these findings suggest that TLX acts as an essential regulator that ensures the proliferative ability of postnatal NSCs by controlling their activation through genetic interaction with p53 and other signaling pathways.

  18. Cholecalciferol (vitamin D₃ improves myelination and recovery after nerve injury.

    Directory of Open Access Journals (Sweden)

    Jean-Francois Chabas

    Full Text Available Previously, we demonstrated i that ergocalciferol (vitamin D2 increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii that cholecalciferol (vitamin D3 improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle, and compared to unlesioned rats (Control. Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day, cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i the number of preserved or newly formed axons in the proximal end, ii the mean axon diameter in the distal end, and iii neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral

  19. Subtle changes in myelination due to childhood experiences: label-free microscopy to infer nerve fibers morphology and myelination in brain (Conference Presentation)

    Science.gov (United States)

    Gasecka, Alicja; Tanti, Arnaud; Lutz, Pierre-Eric; Mechawar, Naguib; Cote, Daniel C.

    2017-02-01

    Adverse childhood experiences have lasting detrimental effects on mental health and are strongly associated with impaired cognition and increased risk of developing psychopathologies. Preclinical and neuroimaging studies have suggested that traumatic events during brain development can affect cerebral myelination particularly in areas and tracts implicated in mood and emotion. Although current neuroimaging techniques are quite powerful, they lack the resolution to infer myelin integrity at the cellular level. Recently demonstrated coherent Raman microscopy has accomplished cellular level imaging of myelin sheaths in the nervous system. However, a quantitative morphometric analysis of nerve fibers still remains a challenge. In particular, in brain, where fibres exhibit small diameters and varying local orientation. In this work, we developed an automated myelin identification and analysis method that is capable of providing a complete picture of axonal myelination and morphology in brain samples. This method performs three main procedures 1) detects molecular anisotropy of membrane phospholipids based on polarization resolved coherent Raman microscopy, 2) identifies regions of different molecular organization, 3) calculates morphometric features of myelinated axons (e.g. myelin thickness, g-ratio). We applied this method to monitor white matter areas from suicides adults that suffered from early live adversity and depression compared to depressed suicides adults and psychiatrically healthy controls. We demonstrate that our method allows for the rapid acquisition and automated analysis of neuronal networks morphology and myelination. This is especially useful for clinical and comparative studies, and may greatly enhance the understanding of processes underlying the neurobiological and psychopathological consequences of child abuse.

  20. Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence.

    Science.gov (United States)

    Lutz, Pierre-Eric; Tanti, Arnaud; Gasecka, Alicja; Barnett-Burns, Sarah; Kim, John J; Zhou, Yi; Chen, Gang G; Wakid, Marina; Shaw, Meghan; Almeida, Daniel; Chay, Marc-Aurele; Yang, Jennie; Larivière, Vanessa; M'Boutchou, Marie-Noël; van Kempen, Léon C; Yerko, Volodymyr; Prud'homme, Josée; Davoli, Maria Antonietta; Vaillancourt, Kathryn; Théroux, Jean-François; Bramoullé, Alexandre; Zhang, Tie-Yuan; Meaney, Michael J; Ernst, Carl; Côté, Daniel; Mechawar, Naguib; Turecki, Gustavo

    2017-12-01

    Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed. The human samples were from depressed individuals who died by suicide, with (N=27) or without (N=25) a history of severe child abuse, as well as from psychiatrically healthy control subjects (N=26). Genome-wide DNA methylation and gene expression were investigated using reduced representation bisulfite sequencing and RNA sequencing, respectively. Cell type-specific validation of differentially methylated loci was performed after fluorescence-activated cell sorting of oligodendrocyte and neuronal nuclei. Differential gene expression was validated using NanoString technology. Finally, oligodendrocytes and myelinated axons were analyzed using stereology and coherent anti-Stokes Raman scattering microscopy. A history of child abuse was associated with cell type-specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional program. These effects were absent in the depressed suicide completers with no history of child abuse, and they were strongly correlated with myelin gene expression changes observed in the animal model. Furthermore, a selective and significant reduction in the thickness of myelin sheaths around small-diameter axons was observed in individuals with history of child abuse. The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a

  1. Neurotoxocarosis alters myelin protein gene transcription and expression.

    Science.gov (United States)

    Heuer, Lea; Beyerbach, Martin; Lühder, Fred; Beineke, Andreas; Strube, Christina

    2015-06-01

    Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p ≤ 0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2', 3 ´-cyclic nucleotide 3'-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas.

  2. Proliferation of Schwann cells induced by axolemmal and myelin membranes

    International Nuclear Information System (INIS)

    Dinneen, M.

    1985-01-01

    Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3 H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80 0 C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100 0 C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

  3. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    The post-natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post...

  4. Live-imaging in the CNS: New insights on oligodendrocytes, myelination, and their responses to inflammation.

    Science.gov (United States)

    Rassul, Sayed Muhammed; Neely, Robert K; Fulton, Daniel

    2016-11-01

    The formation and repair of myelin involves alterations in the molecular and physical properties of oligodendrocytes, and highly coordinated interactions with their target axons. Characterising the nature and timing of these events at the molecular and cellular levels illuminates the fundamental events underlying myelin formation, and provides opportunities for the development of therapies to replace myelin lost through traumatic injury and inflammation. The dynamic nature of these events requires that live-imaging methods be used to capture this information accurately and completely. Developments in imaging technologies, and model systems suitable for their application to myelination, have advanced the study of myelin formation, injury and repair. Similarly, new techniques for single molecule imaging, and novel imaging probes, are providing opportunities to resolve the dynamics of myelin proteins during myelination. Here, we explore these developments in the context of myelin formation and injury, identify unmet needs within the field where progress can be advanced through live-imaging approaches, identify technical challenges that are limiting this progress, and highlight practical applications for these approaches that could lead to therapies for the protection of oligodendrocytes and myelin from injury, and restore myelin lost through injury and disease. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Abundant extracellular myelin in the meninges of patients with multiple sclerosis.

    Science.gov (United States)

    Kooi, E-J; van Horssen, J; Witte, M E; Amor, S; Bø, L; Dijkstra, C D; van der Valk, P; Geurts, J J G

    2009-06-01

    In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. Formalin-fixed brain tissue containing meninges from 29 MS patients, 9 non-neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double-labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non-neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.

  6. Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions.

    Science.gov (United States)

    Yao, Y; Nguyen, T D; Pandya, S; Zhang, Y; Hurtado Rúa, S; Kovanlikaya, I; Kuceyeski, A; Liu, Z; Wang, Y; Gauthier, S A

    2018-02-01

    A hyperintense rim on susceptibility in chronic MS lesions is consistent with iron deposition, and the purpose of this study was to quantify iron-related myelin damage within these lesions as compared with those without rim. Forty-six patients had 2 longitudinal quantitative susceptibility mapping with automatic zero reference scans with a mean interval of 28.9 ± 11.4 months. Myelin water fraction mapping by using fast acquisition with spiral trajectory and T2 prep was obtained at the second time point to measure myelin damage. Mixed-effects models were used to assess lesion quantitative susceptibility mapping and myelin water fraction values. Quantitative susceptibility mapping scans were on average 6.8 parts per billion higher in 116 rim-positive lesions compared with 441 rim-negative lesions ( P quantitative susceptibility mapping values of both the rim and core regions ( P Quantitative susceptibility mapping scans and myelin water fraction in rim-positive lesions decreased from rim to core, which is consistent with rim iron deposition. Whole lesion myelin water fractions for rim-positive and rim-negative lesions were 0.055 ± 0.07 and 0.066 ± 0.04, respectively. In the mixed-effects model, rim-positive lesions had on average 0.01 lower myelin water fraction compared with rim-negative lesions ( P quantitative susceptibility mapping scan was negatively associated with follow-up myelin water fraction ( P Quantitative susceptibility mapping rim-positive lesions maintained a hyperintense rim, increased in susceptibility, and had more myelin damage compared with rim-negative lesions. Our results are consistent with the identification of chronic active MS lesions and may provide a target for therapeutic interventions to reduce myelin damage. © 2018 by American Journal of Neuroradiology.

  7. Prenatal family support, postnatal family support and postpartum depression.

    Science.gov (United States)

    Xie, Ri-Hua; Yang, Jianzhou; Liao, Shunping; Xie, Haiyan; Walker, Mark; Wen, Shi Wu

    2010-08-01

    Inadequate social support is an important determinant of postpartum depression (PPD). Social support for pregnant women consists of supports from various sources and can be measured at different gestation periods. Differentiating the effects of social support from different sources and measured at different gestation periods may have important implications in the prevention of PPD. In the family centred Chinese culture, family support is likely to be one of the most important components in social support. The aim of this study was to assess the association of prenatal family support and postnatal family support with PPD. A prospective cohort study was conducted between February and September 2007 in Hunan, China. Family support was measured with social support rating scale at 30-32 weeks of gestation (prenatal support) and again at 2 weeks of postpartum visit (postnatal support). PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) score > or =13. A total of 534 pregnant women were included, and among them, 103 (19.3%) scored 13 or more on the EPDS. PPD was 19.4% in the lowest tertile versus 18.4% in the highest quartile (adjusted odds ratio: 1.04, 95% confidence interval 0.60, 1.80) for prenatal support from all family members, and PPD was 39.8% in the lowest tertile versus 9.6% in the highest tertile (adjusted odds ratio: 4.4, 95% confidence interval 2.3, 8.4) for postnatal support from all family members. Among family members, support from husband had the largest impact on the risk of developing PPD. Lack of postnatal family support, especially the support from husband, is an important risk factor of PPD.

  8. Staining Methods for Normal and Regenerative Myelin in the Nervous System.

    Science.gov (United States)

    Carriel, Víctor; Campos, Antonio; Alaminos, Miguel; Raimondo, Stefania; Geuna, Stefano

    2017-01-01

    Histochemical techniques enable the specific identification of myelin by light microscopy. Here we describe three histochemical methods for the staining of myelin suitable for formalin-fixed and paraffin-embedded materials. The first method is conventional luxol fast blue (LFB) method which stains myelin in blue and Nissl bodies and mast cells in purple. The second method is a LBF-based method called MCOLL, which specifically stains the myelin as well the collagen fibers and cells, giving an integrated overview of the histology and myelin content of the tissue. Finally, we describe the osmium tetroxide method, which consist in the osmication of previously fixed tissues. Osmication is performed prior the embedding of tissues in paraffin giving a permanent positive reaction for myelin as well as other lipids present in the tissue.

  9. Guanine nucleotides stimulate hydrolysis of phosphatidyl inositol bis phosphate in human myelin membranes

    International Nuclear Information System (INIS)

    Boulias, C.; Moscarello, M.A.

    1989-01-01

    Phosphodiesterase activity was stimulated in myelin membranes in the presence of guanine nucleotide analogues. This activity was reduced in myelin membranes which had been adenosine diphosphate ribosylated in the presence of cholera toxin which ADP-ribosylated three proteins of Mr 46,000, 43,000 and 18,500. Aluminum fluoride treatment of myelin had the same stimulatory effects on phosphodiesterase activity as did the guanine nucleotides

  10. Endogenous phosphorylation of basic protein in myelin of varying degrees of compaction

    International Nuclear Information System (INIS)

    Schulz, P.; Moscarello, M.A.; Cruz, T.F.

    1988-01-01

    Fractions containing myelin of varying degrees of compaction were prepared from human white matter. Protein kinase activity in these fractions was measured by using both endogenous and exogenous myelin basic protein (MBP) as substrates. In both cases, less compact myelin fractions possessed higher levels of protein kinase activity than the compact myelin fraction. In addition, the specific activity of phosphorylated basic protein was greater in the loosely compacted fractions than in compact multilamellar myelin. When basic protein in compact myelin or the myelin fractions was phosphorylated by the endogenous kinase, approximately 70% of the [ 32 P]phosphate was incorporated at a single site, identified as Ser-102. The remaining 30% was found in three other minor sites. Electron microscopy of less compact myelin showed it was composed of fewer lamellae which correlated with a relative decrease in the proportion of cationic charge isomers (microheteromers) when MBP was subjected to gel electrophoresis at alkaline pH. The shift in charge microheterogeneity of basic protein to the less cationic isomers in the less compact myelin fractions correlated with an increase in protein kinase activity and a greater specific activity of phosphorylated basic protein

  11. Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance.

    Science.gov (United States)

    Brazhe, A R; Maksimov, G V; Mosekilde, E; Sosnovtseva, O V

    2011-02-06

    The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

  12. The structural and functional role of myelin fast-migrating cerebrosides

    DEFF Research Database (Denmark)

    Podbielska, Maria; Levery, Steven B; Hogan, Edward L

    2011-01-01

    A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds...... myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases...

  13. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

    Science.gov (United States)

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

    2011-03-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

  14. Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2 receptors and of NT1 receptors in the rat brain revealed by in situ hybridization.

    Science.gov (United States)

    Lépée-Lorgeoux, I; Betancur, C; Rostène, W; Pélaprat, D

    1999-03-12

    The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development. Copyright 1999 Elsevier Science B.V.

  15. Rapid myelin water imaging in human cervical spinal cord.

    Science.gov (United States)

    Ljungberg, Emil; Vavasour, Irene; Tam, Roger; Yoo, Youngjin; Rauscher, Alexander; Li, David K B; Traboulsee, Anthony; MacKay, Alex; Kolind, Shannon

    2017-10-01

    Myelin water imaging (MWI) using multi-echo T 2 relaxation is a quantitative MRI technique that can be used as an in vivo biomarker for myelin in the central nervous system. MWI using a multi-echo spin echo sequence currently takes more than 20 min to acquire eight axial slices (5 mm thickness) in the cervical spinal cord, making spinal cord MWI impractical for implementation in clinical studies. In this study, an accelerated gradient and spin echo sequence (GRASE), previously validated for brain MWI, was adapted for spinal cord MWI. Ten healthy volunteers were scanned with the GRASE sequence (acquisition time 8.5 min) and compared with the multi-echo spin echo sequence (acquisition time 23.5 min). Using region of interest analysis, myelin estimates obtained from the two sequences were found to be in good agreement (mean difference = -0.0092, 95% confidence interval =  - 0.0092 ± 0.061; regression slope = 1.01, ρ = 0.9). MWI using GRASE was shown to be highly reproducible with an average coefficient of variation of 6.1%. The results from this study show that MWI can be performed in the cervical spinal cord in less than 10 min, allowing for practical implementation in multimodal clinical studies. Magn Reson Med 78:1482-1487, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  16. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

    Directory of Open Access Journals (Sweden)

    Cecilie Linneberg

    2015-09-01

    Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  17. Postnatally acquired cytomegalovirus infections in preterm infants

    NARCIS (Netherlands)

    Nijman, J.

    2013-01-01

    A postnatal cytomegalovirus (CMV) infection is common in very low birth weight infants with an estimated prevalence of 6–59%. Breast milk from CMV seropositive mothers is the main source of postnatal CMV infection. Ninety-six percent of these mothers shed CMV in their breast milk after delivery due

  18. Morphological observations on the metanephros in the postnatal opossum, Didelphis virginiana.

    Science.gov (United States)

    Krause, W J; Cutts, J H; Leeson, C R

    1979-10-01

    The metanephros of the newborn opossum is very immature, consisting only of collecting tubules and a few immature nephrons. Development during the postnatal period can be divided into two distinct phases. The initial phase occurs during the first 60 days of postnatal life and is concerned with nephronogenesis and the differentiation of nephrons that have formed during this period. The second phase lasts through the remainder of the postnatal period and is concerned with further differentiation and growth of established nephrons. During this latter period the tubular portion of the nephron increases in length and the renal corpuscle increases in diameter. Ultrastructural observations suggest that metanephric nephrons are not functional during the first 4 days of postnatal life, while the mesonephros reaches the height of its development during this period: there may be some functional overlap between the mesonephros and metanephros during the latter part of the first week of postnatal life. The pattern of nephron induction and differentiation in the opossum is discussed.

  19. MAL Is a Regulator of the Recruitment of Myelin Protein PLP to Membrane Microdomains

    NARCIS (Netherlands)

    Bijlard, Marjolein; de Jonge, Jenny C.; Klunder, Bert; Nomden, Anita; Hoekstra, Dick; Baron, Wia

    2016-01-01

    In oligodendrocytes (OLGs), an indirect, transcytotic pathway is mediating transport of de novo synthesized PLP, a major myelin specific protein, from the apical-like plasma membrane to the specialized basolateral-like myelin membrane to prevent its premature compaction. MAL is a well-known

  20. Direct visualization of membrane architecture of myelinating cells in transgenic mice expressing membrane-anchored EGFP.

    Science.gov (United States)

    Deng, Yaqi; Kim, BongWoo; He, Xuelian; Kim, Sunja; Lu, Changqing; Wang, Haibo; Cho, Ssang-Goo; Hou, Yiping; Li, Jianrong; Zhao, Xianghui; Lu, Q Richard

    2014-04-01

    Myelinogenesis is a complex process that involves substantial and dynamic changes in plasma membrane architecture and myelin interaction with axons. Highly ramified processes of oligodendrocytes in the central nervous system (CNS) make axonal contact and then extrapolate to wrap around axons and form multilayer compact myelin sheathes. Currently, the mechanisms governing myelin sheath assembly and axon selection by myelinating cells are not fully understood. Here, we generated a transgenic mouse line expressing the membrane-anchored green fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP expression is driven by the promoter of 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression defines the inner layers of myelin sheaths and Schmidt-Lanterman incisures in adult sciatic nerves. In addition, mEGFP expression can be used to track the extent of remyelination after demyelinating injury in a toxin-induced demyelination animal model. Taken together, the membrane-anchored mEGFP expression in the new transgenic line would facilitate direct visualization of dynamic myelin membrane formation and assembly during development and process remodeling during remyelination after various demyelinating injuries.

  1. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    Science.gov (United States)

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  2. On the biogenesis of the myelin sheath : Cognate polarized trafficking pathways in oligodendrocytes

    NARCIS (Netherlands)

    de Vries, H; Hoekstra, D

    2000-01-01

    Oligodendrocytes, the myelinating cells of the central nervous system, are capable of transporting vast quantities of proteins and of lipids, In particular galactosphingolipids, to the myelin sheath. The sheath is continuous with the plasma membrane of the oligodendrocyte, but the composition of

  3. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

    NARCIS (Netherlands)

    Chrast, R.; Saher, G.; Nave, K.A.; Verheijen, M.H.G.

    2011-01-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid

  4. Effects of myelin or cell body brainstem lesions on 3-channel Lissajous' trajectories of feline auditory brainstem evoked potentials.

    Science.gov (United States)

    Pratt, H; Zaaroor, M; Bleich, N; Starr, A

    1991-06-01

    Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats to obtain 3-Channel Lissajous' Trajectories (3CLTs) using three orthogonal differential electrode configurations (nasion-midline nuchal ridge, left-right mastoids, vertex-midline under the mandible). Potentials, evoked by monaural 80 dBnHL (re, human threshold) clicks, were studied before, and up to 7 weeks after inducing neuronal lesions localized to the cochlear nucleus (CN) or the superior olivary complex (SOC), or myelin lesions localized to the fibers of the trapezoid body connecting these two structures. Neuronal lesions were induced by injection of kainic acid (KA), while myelin lesions were induced by injection of L-alpha-lysophosphatidylcholine (LPC). With CN neuronal lesions the major changes in 3CLT were in the time domain of 'b', 'c' and 'd' (components P2, P3 and P4 of single-channel ABEP). With SOC neuronal lesions the major changes were in 'c' and 'd' of 3CLT (P3 and P4 of ABEP). With trapezoid body lesions the major change was in 'c' (P3 of ABEP). The results are compatible with the peripheral generation of the first ABEP components (P1a and P1b). The second component (P2) is generated by ipsilateral CN neurones and their outputs. The third component (P3) is generated primarily by ipsilateral SOC neurones and their outputs, with the ipsilateral CN providing input. The The fourth component (P4) is generated bilaterally by the SOC neurones and their outputs, receiving their inputs from ipsilateral CN. The fifth ABEP component (P5) is generated by structures central to the SOCs and their immediate outputs. Neither focal neuronal nor myelin lesions were sufficient to produce obliteration of any component, consistent with a set of generators for each of the ABEP components, consisting of both cell bodies and their output fibers, that is distributed spatially in the brainstem.

  5. Exploitation of detergent thermodynamics in the direct solubilization of myelin membrane proteins for two-dimensional gel electrophoresis for proteomic analysis.

    Science.gov (United States)

    Nair, Sreepriya; Xavier, Tessy; Kumar, Madathiparambil Kumaran Satheesh; Saha, Sharmistha; Menon, Krishnakumar N

    2011-12-01

    Performing 2-DE of lipid-rich multilamellar membranes like myelin is a cumbersome task. However, for understanding its molecular organization and changes during diseases, identification of proteins of myelin is essential. Although the 2-D-proteomic approach of myelin has been employed to understand the myelin proteome, representation of myelin proteins in its entirety is still a challenge. 2-DE profiling of myelin proteins is very important for the detection of immuno-reactivity to myelin proteins from various biological fluids following Western blotting in diseases like multiple sclerosis. Here we developed a novel approach by exploiting the thermodynamic principles behind detergent-mediated solubilization of myelin membranes without any conventional processing of myelin involving precipitation of myelin proteins. We show that the addition of myelin to ASB-14-4 resulted in significant increase in protein representation of myelin in 2-DE compared with the addition of ASB-14-4 to myelin. Moreover, the number and resolution of spots are significantly higher in myelin to ASB-14-4 strategy than other strategies of myelin sample processing such as ASB-14-4 to myelin or ethanol or acetone or methanol-ammonium acetate precipitation of myelin proteins. In addition, the step involves no precipitation that selective removal of any proteins as a result of precipitation is nil and a qualitative representation of myelin proteins in a 2-D gel is achieved. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Yeste, Ada; Nadeau, Meghan; Burns, Evan J.; Weiner, Howard L.; Quintana, Francisco J.

    2012-01-01

    The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+ Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55 expanded the FoxP3+ Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders. PMID:22745170

  7. A quantitative measure of myelination development in infants, using MR images

    Energy Technology Data Exchange (ETDEWEB)

    Carmody, Dennis P. [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Dunn, Stanley M.; Boddie-Willis, Akiza S. [The State University of New Jersey, Rutgers, New Brunswick, NJ (United States); DeMarco, J. Kevin [Laurie Imaging Center, New Brunswick, NJ (United States); Lewis, Michael [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Institute for the Study of Child Development, New Brunswick (United States)

    2004-09-01

    The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

  8. A quantitative measure of myelination development in infants, using MR images

    International Nuclear Information System (INIS)

    Carmody, Dennis P.; Dunn, Stanley M.; Boddie-Willis, Akiza S.; DeMarco, J. Kevin; Lewis, Michael

    2004-01-01

    The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

  9. The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

    OpenAIRE

    Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

    2017-01-01

    Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidate...

  10. Plasma myelin basic protein assay using Gilford enzyme immunoassay cuvettes.

    Science.gov (United States)

    Groome, N P

    1981-10-01

    The assay of myelin basic protein in body fluids has potential clinical importance as a routine indicator of demyelination. Preliminary details of a competitive enzyme immunoassay for this protein have previously been published by the author (Groome, N. P. (1980) J. Neurochem. 35, 1409-1417). The present paper now describes the adaptation of this assay for use on human plasma and various aspects of routine data processing. A commercially available cuvette system was found to have advantages over microtitre plates but required a permuted arrangement of sample replicates for consistent results. For dose interpolation, the standard curve could be fitted to a three parameter non-linear equation by regression analysis or linearised by the logit/log transformation.

  11. Revealing tact within postnatal care.

    Science.gov (United States)

    Smythe, Elizabeth; Payne, Deborah; Wilson, Sally; Paddy, Ann; Heard, Kate

    2014-02-01

    In this article, we explore the nature of good postnatal care through a hermeneutic unpacking of the notion of tact, drawing on the philosophical writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered were from a hermeneutic research study within a small, rural birthing center in New Zealand. Insights drawn from the analysis were as follows: the openness of listening, watching and being attuned that builds a positive mode of engagement, recognizing that the distance the woman needs from her nurse/midwife is a call of tact, that tact is underpinned by a spirit of care, within tact there are moods and tact might require firmness, and that all of these factors come together to build trust. We conclude that the attunement of tact requires that the staff member has time to spend with a woman, enough energy to engage, and a spirit of care. Women know that tactful practice builds their confidence and affects their mothering experience. Tact cannot be assumed; it needs to be nurtured and sheltered.

  12. Heterogeneity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging.

    Directory of Open Access Journals (Sweden)

    Tobias Djamsched Faizy

    Full Text Available To assess neuroprotection and remyelination in Multiple Sclerosis (MS, we applied a more robust myelin water imaging (MWI processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC.Seventeen MS-patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI examination including MWI (8 slices, 12 minutes acquisition time, T2w and T1mprage pre and post gadolinium (GD administration. Black holes (BH, contrast enhancing lesions (CEL and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI were defined in the frontal, parietal and occipital normal appearing white matter (NAWM/white matter (WM, the corticospinal tract (CST, the splenium (SCC and genu (GCC of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF were determined for each ROI.Significant differences (p≤0.05 of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions, compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p≤0.05 difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF.MWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls.

  13. Normal variation of focal T2 Hyperintensities in anterior parietal periventricular white matter: Another 'Terminal Zones of Myelination'

    International Nuclear Information System (INIS)

    Park, Jong Oag; Woo, Je Ho; Ki, Tae Sung; Lee, Jong Hwa; Chung, Jin Woo; Lee, Don Young

    1994-01-01

    It has been known that there are several areas of T2 hyperintensity in normal white matter of brain, such as terminal zones of myelination, ependymitis granularis, ones of posterior internal capsule, and perivascular space. The aim of our study is to demonstrate another region of T2 hyperintensities in normal pediatric age group. We have studied brain MR for 10 normal volunteers and 35 patients without having intracranial lesions in pediatric age group(3-19 years). In 5 among 45 cases, focal T2 hyperintensities were seen in the parietal periventricular white matter beneath the postcentral gyri. They were noted as poorly defined, 5-10 mm sized areas of increased signal intensities on T2-weighted axial images. They were also characterized by bilateral, posteromedially oriented, short band-like or oval areas. Interestingly, they were directly continuous with the T2 hyperintensity of posterior internal capsule. In spite of the relatively highly frequency in the pediatric population as in our study, this finding has not been reported in the asymptomatic adults. The results show that the bilateral anterior parietal hyperintense areas may be another terminal zones of delayed myelination affecting the parietopontine tract. They should be differentiated from pathologic T2 hyperintensities by their characteristic findings

  14. Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

    Science.gov (United States)

    Ino, Daisuke; Sagara, Hiroshi; Suzuki, Junji; Kanemaru, Kazunori; Okubo, Yohei; Iino, Masamitsu

    2015-09-29

    Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Is There Evidence for Myelin Modeling by Astrocytes in the Normal Adult Brain?

    Directory of Open Access Journals (Sweden)

    Alfredo Varela-Echevarría

    2017-09-01

    Full Text Available A set of astrocytic process associated with altered myelinated axons is described in the forebrain of normal adult rodents with confocal, electron microscopy, and 3D reconstructions. Each process consists of a protuberance that contains secretory organelles including numerous lysosomes which polarize and open next to disrupted myelinated axons. Because of the distinctive asymmetric organelle distribution and ubiquity throughout the forebrain neuropil, this enlargement is named paraxial process (PAP. The myelin envelope contiguous to the PAP displays focal disruption or disintegration. In routine electron microscopy clusters of large, confluent, lysosomes proved to be an effective landmark for PAP identification. In 3D assemblies lysosomes organize a series of interconnected saccules that open up to the plasmalemma next to the disrupted myelin envelope(s. Activity for acid hydrolases was visualized in lysosomes, and extracellularly at the PAP-myelin interface and/or between the glial and neuronal outer aspects. Organelles in astrocytic processes involved in digesting pyknotic cells and debris resemble those encountered in PAPs supporting a likewise lytic function of the later. Conversely, processes entangling tripartite synapses and glomeruli were devoid of lysosomes. Both oligodendrocytic and microglial processes were not associated with altered myelin envelopes. The possible roles of the PAP in myelin remodeling in the context of the oligodendrocyte-astrocyte interactions and in the astrocyte's secretory pathways are discussed.

  16. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    Directory of Open Access Journals (Sweden)

    Roberta Noseda

    2016-04-01

    Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

  17. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

    Science.gov (United States)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  18. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

    Science.gov (United States)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  19. Experiment on radiotherapy of postnatal mastitis

    International Nuclear Information System (INIS)

    Zhut'ko, A.A.

    1978-01-01

    The results of radiotherapy of postnatal mastitis in 78 women are presented. It is shown that the radiotherapy is the method of choice. Application of radiotherapy at different stages of disease promotes either complete resolution of infiltration (1-2 irradiations) or stipulates the decrease in temperature, abatement of pains and improvement of general state (at the presence of purulent fusion of mammary tissue). X-ray therapy of postnatal mastitis has does not affect the lactational function of mammary gland

  20. Postnatal depression: a review of recent literature.

    OpenAIRE

    Richards, J P

    1990-01-01

    Depression affects 5-22% of women after childbirth. Some women with postnatal depression will experience a prolonged or relapsing illness that may last until their children enter school. It has adverse effects upon the coping abilities of women, their relationships with their infants, partners and social networks and may adversely affect the educational attainment and behaviour of their children. Since many more women are now active in the workforce, the effects of postnatal depression have o...

  1. MR imaging of the various stages of normal myelination during the first year of life

    International Nuclear Information System (INIS)

    Knaap, M.S. van der; Valk, J.

    1990-01-01

    The normal process of myelination of the brain mainly occurs during the first year of life. This process as known from histology can be visualized by MRI. Because of the very long T1 and T2 of immature brain tissue it is necessary to use adjusted pulse sequences with a long TR in order to obtain sufficient tissue contrast. With long TR SE images five stages can be recognized in the process of normal myelination and brain maturation. During the first month of life long TR short TE SE images show what are believed to be myelinated structures by correlation with published histological studies with a high signal intensity, unmyelinated white matter with a low signal intensity and gray matter with an intermediate signal intensity. The signal intensity of unmyelinated and myelinated white matter is reversed on long TR long TE SE images. In the course of a few weeks the signal intensity of unmyelinated white matter becomes high and the signal intensity of myelinated white matter becomes low also on long TR short TE SE images. These changes are believed to be caused by a loss of water and a change in chemical composition of brain tissue just prior to the onset of a wave of myelination. With progression of myelination the signal intensity of white matter changes from high to intermediate to low. These changes result in stages of isointensity, first in the central parts of the brain, later in the lobar parts. At the end of the first year the adult contrast pattern is reached in all parts of the brain. IR images are also able to depict the progress of myelination, but appear to be less sensitive to subtle changes in the degree of myelination. The precise normal values for the five stages depend on the magnetic field strength and the pulse sequences used. (orig.)

  2. Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system.

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2010-02-01

    Full Text Available Inflammatory response following central nervous system (CNS injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS and its animal model, experimental autoimmune encephalomyelitis (EAE, there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI, i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-kappaB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-kappaB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin and myelin basic protein (MBP, one of the major proteins of myelin are not able to activate NF-kappaB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI.

  3. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    Science.gov (United States)

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis.

    Science.gov (United States)

    Nakajima, Hideki; Motomura, Masakatsu; Tanaka, Keiko; Fujikawa, Azusa; Nakata, Ruka; Maeda, Yasuhiro; Shima, Tomoaki; Mukaino, Akihiro; Yoshimura, Shunsuke; Miyazaki, Teiichiro; Shiraishi, Hirokazu; Kawakami, Atsushi; Tsujino, Akira

    2015-04-02

    To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON. We recruited participants in the department of neurology and ophthalmology in our hospital in Japan. We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay. Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16-84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald's criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16-84 years). 27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy. Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON

  5. X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

    Science.gov (United States)

    Chia, L S; Thompson, J E; Moscarello, M A

    1984-09-05

    Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

  6. Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors.

    Directory of Open Access Journals (Sweden)

    Ekaterina E Verdiyan

    Full Text Available In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC acetylcholine receptors (AChRs and the axon excitation (different intervals between action potentials (APs. Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the "axon-SC" interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+-influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization.

  7. Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

    Directory of Open Access Journals (Sweden)

    Laulumaa Saara

    2015-01-01

    Full Text Available Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

  8. Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia

    DEFF Research Database (Denmark)

    Dionne, Nancy; Dib, Samar; Finsen, Bente

    2016-01-01

    regulatory element combinations were found to drive expression in oligodendrocytes and Schwann cells with a minimal 129 bp sequence conferring expression in oligodendrocytes throughout myelin elaboration, maintenance and repair. Unexpectedly, M3 derivatives conferred markedly different spatial and temporal...

  9. Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

    Science.gov (United States)

    Laulumaa, Saara; Kursula, Petri; Natali, Francesca

    2015-01-01

    Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

  10. Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study

    NARCIS (Netherlands)

    Hendriks, Jerome J. A.; de Vries, Helga E.; van der Pol, Susanne M. A.; van den Berg, Timo K.; van Tol, Eric A. F.; Dijkstra, Christine D.

    2003-01-01

    Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds,

  11. The MR evaluation of normal children and disorders of neuronal migration and myelination

    International Nuclear Information System (INIS)

    Miyamachi, Keikichi; Miyasaka, Kazuo; Abe, Hiroshi

    1990-01-01

    Magnetic resonance imaging (MRI) scans were available for review in 10 healthy children (aged one month-4 years) and 5 pediatric patients with disorders of neuronal migration and myelination during the developing process (aged 2-10 years). Such disorders in the 5 patients were megalencephaly, pachygyria, heterotopia, delayed myelination, and dysmyelinating disease. In the heathy group, myelination was matured during the first two years on MRI. This was depicted earlier on T1-weighted images than T2-weighted images (7 months vs one year and 9 months after birth). Abnormality in myelination was clearly visualized on T2-weighted images. Furthermore, MRI had the ability to detect morphologically the associated brain malformations. Thus, MRI may be a promising diagnostic procedure of choice in pediatric brain abnormality. (N.K.)

  12. A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity.

    Science.gov (United States)

    Kassmann, Celia M; Quintes, Susanne; Rietdorf, Jens; Möbius, Wiebke; Sereda, Michael Werner; Nientiedt, Tobias; Saher, Gesine; Baes, Myriam; Nave, Klaus-Armin

    2011-07-21

    Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Splanchnic preganglionic neurons in man. III. Morphometry of myelinated fibers of rami communicantes.

    Science.gov (United States)

    Low, P A; Dyck, P J

    1978-01-01

    The myelinated fiber (MF) composition of T6-T8 Rami Communicantes were obtained in 9 healthy persons of various ages. The textbook picture that distal rami (DR) contain all of the myelinated fibers and therefore are white, while proximal rami (PR) contain none of them and therefore are grey must be modified. We found that DR usually contained abundant MFs and that PR concordance was found between segmental numbers of intermediolateral nuclei cytons, ventral root small myelinated fibers (SMFs), and rami total small MFs to suggest that both rami probably contain the distal myelinated axons of preganglionic autonomic fibers. Finally, there was an attrition of total MFs of rami with age, similar to what we had previously found for ILC cytons and for root SMFs. The decrease in number of pre-ganglionic autonomic neurons with age is thought to be of sufficient magnitude to account for the dysautonomia of the elderly.

  14. The development of the cholinergic system in rat hippocampus following postnatal X-irradiation

    International Nuclear Information System (INIS)

    Ben-Barak, J.

    1981-01-01

    Postnatal X-irradiation of the rat hippocampus results in a marked reduction in the number of the postnatally developing granular neurons in the dentate gyrus and also caused a marked increase in the specific activity of acetylcholinesterase (AChE) and choline acetyltransferase (CAT) and a slight but consistent increase in the activity per whole hippocampus of AChE. The effect of irradiation on the granular neurons and on the cholinergic enzymes was found to be dose and age dependent. Drastic increase in specific enzymatic activities is also observed in the irradiated cerebellum whose granular neurons differentiate postnatally and to a lesser extent in the cerebral cortex in which cell formation is accomplished prior to birth. (Auth.)

  15. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

    Directory of Open Access Journals (Sweden)

    Hadas Smadar

    2012-07-01

    Full Text Available Abstract Background Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3 is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin remodeling (i.e., disassembly and reassembly by shifting between active unphosphorylated and inactive phosphorylated states. Results Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia, which, as we also revealed, are instrumental in myelin phagocytosis. Conclusions CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive

  16. Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

    Science.gov (United States)

    Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

    2017-09-01

    To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

  17. Type a niemann-pick disease. Description of three cases with delayed myelination.

    Science.gov (United States)

    D'Amico, A; Sibilio, M; Caranci, F; Bartiromo, F; Taurisano, R; Balivo, F; Melis, D; Parenti, G; Cirillo, S; Elefante, R; Brunetti, A

    2008-06-03

    We describe three patients with type A Niemann-Pick disease (NPD-A). NPD-A is an autosomal recessive neuronal storage disease classified among the sphingolipidoses, characterized by accumulation of sphingomyelin in various tissues and in the brain. Magnetic Resonance imaging (MRI) of our three patients showed a marked delay of myelination with frontal atrophy. Few descriptions of this MRI pattern of delayed myelination have been published to date.

  18. Early myelin breakdown following sural nerve crush: a freeze-fracture study

    Directory of Open Access Journals (Sweden)

    Martinez A.M.B.

    2000-01-01

    Full Text Available In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

  19. Extended postnatal brain development in the longest-lived rodent: prolonged maintenance of neotenous traits in the naked mole-rat brain

    Directory of Open Access Journals (Sweden)

    Miranda E. Orr

    2016-11-01

    Full Text Available The naked mole-rat (NMR is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to three years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At four months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until nine months of age in NMRs, and synaptic protein expression continues to change throughout the first three years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through six weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short

  20. Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain.

    Science.gov (United States)

    Orr, Miranda E; Garbarino, Valentina R; Salinas, Angelica; Buffenstein, Rochelle

    2016-01-01

    The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.

  1. Crystal structure of the extracellular domain of human myelin protein zero

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

    2012-03-27

    Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125

  2. Classic and Golli Myelin Basic Protein have distinct developmental trajectories in human visual cortex.

    Science.gov (United States)

    Siu, Caitlin R; Balsor, Justin L; Jones, David G; Murphy, Kathryn M

    2015-01-01

    Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a "molecular link" between the nervous and immune systems. In visual cortex specifically, myelin proteins interact with immune processes to affect experience-dependent plasticity. We studied myelin in human visual cortex using Western blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue samples ranging in age from 20 days to 80 years. We found that Classic- and Golli-MBP have different patterns of change across the lifespan. Classic-MBP gradually increases to 42 years and then declines into aging. Golli-MBP has early developmental changes that are coincident with milestones in visual system sensitive period, and gradually increases into aging. There are three stages in the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli-MBP has a wave of high inter-individual variability during childhood. These results about cortical MBP expression are timely because they compliment recent advances in MRI techniques that produce high resolution maps of cortical myelin in normal and diseased brain. In addition, the unique pattern of Golli-MBP expression across the lifespan suggests that it supports high levels of neuroimmune interaction in cortical development and in aging.

  3. Impairment of heme synthesis in myelin as potential trigger of multiple sclerosis.

    Science.gov (United States)

    Morelli, Alessandro; Ravera, Silvia; Calzia, Daniela; Panfoli, Isabella

    2012-06-01

    The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS. According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Prenatal music stimulation facilitates the postnatal functional ...

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... In chickens, postnatal short-term exposure to rhythmic musical stimuli ..... Exposure to music has long been associated with enhance cognitive abilities in ... memory performance in the T-maze task (Chaudhury et al. 2010, Sanyal et al. .... children with ADHD and nondisabled children. J. Learn. Disabil.

  5. Radiology of postnatal skeletal development. Pt. 7

    International Nuclear Information System (INIS)

    Ogden, J.A.; Phillips, S.B.

    1983-01-01

    Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence. (orig.)

  6. Postnatal depression, oxytocin and maternal sensitivity

    NARCIS (Netherlands)

    Mah, Beth Lynette

    2015-01-01

    Intra nasal oxytocin administered to a population of mothers with a diagnosis of postnatal depression: -lowers their current mood -causes mothers to report that their infants are more difficult but their relationship with them is more positive -increases their protective response towards them in the

  7. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen

    2008-01-01

    protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic...

  8. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime

    Energy Technology Data Exchange (ETDEWEB)

    Knoll, W. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Peters, J. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Institut de Biologie Structurale, Grenoble (France); Kursula, P. [University of Oulu, Oulu (Finland); CSSB–HZI, DESY, Hamburg (Germany); Gerelli, Y. [Institut Laue–Langevin, Grenoble (France); Natali, F., E-mail: natali@ill.fr [Institut Laue–Langevin, Grenoble (France); CNR–IOM–OGG, c/o Institut Laue–Langevin, Grenoble (France)

    2014-11-28

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

  9. Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Möbius, Wiebke; Wehr, Michael C; Krämer-Albers, Eva-Maria; Brügger, Britta; Nave, Klaus-Armin

    2009-05-13

    Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. Because many myelin proteins partition into cholesterol-rich membrane rafts, their interaction with cholesterol could potentially be part of the ER quality control system. Here, we provide in vitro and in vivo evidence that the major peripheral myelin protein P0 requires cholesterol for exiting the ER and reaching the myelin compartment. Cholesterol dependency of P0 trafficking in heterologous cells is mediated by a cholesterol recognition/interaction amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol biosynthesis in Schwann cells suffer from severe hypomyelination with numerous uncompacted myelin stretches. This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction.

  10. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.

    Science.gov (United States)

    Al Jaam, Bilal; Heu, Katy; Pennarubia, Florian; Segelle, Alexandre; Magnol, Laetitia; Germot, Agnès; Legardinier, Sébastien; Blanquet, Véronique; Maftah, Abderrahman

    2016-09-01

    Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/cax) mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1(cax/cax) SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7(+)/MYOD(-) progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice. © 2016 The Authors.

  11. HIV/AIDS and Postnatal Depression at the University Teaching ...

    African Journals Online (AJOL)

    Objective: To study the contribution of HIV/AIDS to the problem of postnatal depression among women receiving postnatal care at University Teaching Hospital (UTH), Lusaka, Zambia. Background: Postnatal depression (PND), a major depressive episode during the puerperium, affects between 10% and 22% of adult ...

  12. How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses.

    Science.gov (United States)

    Tomassy, Giulio Srubek; Fossati, Valentina

    2014-01-01

    Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any possible aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations, and their progenitors, is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS), oligodendrocytes (OLs) are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering

  13. How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses.

    Directory of Open Access Journals (Sweden)

    Giulio eSrubek Tomassy

    2014-07-01

    Full Text Available Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS, oligodendrocytes (OLs are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity

  14. Cthrc1 is a negative regulator of myelination in Schwann cells.

    Science.gov (United States)

    Apra, Caroline; Richard, Laurence; Coulpier, Fanny; Blugeon, Corinne; Gilardi-Hebenstreit, Pascale; Vallat, Jean-michel; Lindner, Volkhard; Charnay, Patrick; Decker, Laurence

    2012-03-01

    The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

  15. Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease

    Science.gov (United States)

    Shi, Riyi; Page, Jessica; Tully, Melissa

    2016-01-01

    Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and organ systems they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and instigator of oxidative stress, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models by conserving myelin structural integrity and alleviating functional deficits. This evidence is indicative that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease. PMID:25879847

  16. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

    Science.gov (United States)

    Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

    2018-02-13

    Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

  17. Molecular architecture of myelinated nerve fibers: leaky paranodal junctions and paranodal dysmyelination.

    Science.gov (United States)

    Rosenbluth, Jack; Mierzwa, Amanda; Shroff, Seema

    2013-12-01

    Myelinated nerve fibers have evolved to optimize signal propagation. Each myelin segment is attached to the axon by the unique paranodal axoglial junction (PNJ), a highly complex structure that serves to define axonal ion channel domains and to direct nodal action currents through adjacent nodes. Surprisingly, this junction does not entirely seal the paranodal myelin sheath to the axon and thus does not entirely isolate the perinodal space from the internodal periaxonal space. Rather the paranode is penetrated by extracellular pathways between the myelin sheath and the axolemma for movement of molecules and the flow of current to and from the internodal axon. This review summarizes past and current studies demonstrating these pathways and considers what functional roles they subserve. In addition, modern genetic engineering methods permit modification of individual PNJ constituents, which provides an opportunity to define their specific functions. One component in particular, the transverse bands, plays a key role in maintaining the structure and function of the PNJ. Loss of transverse bands results not in frank demyelination but rather in subtle dysmyelination, which causes significant functional impairment. The consequences of such subtle defects in the PNJ are considered along with the relevance of these studies to human diseases of myelin.

  18. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    Science.gov (United States)

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2017-11-01

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase

    Directory of Open Access Journals (Sweden)

    Gieselmann Volkmar

    2011-03-01

    Full Text Available Abstract Background The sphingolipids galactosylceramide (GalCer and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt-/- mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h gene. Results Fa2h-/-/Cgt-/- double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to Cgt-/- mice the amount of GlcCer in CNS myelin was strongly reduced in Fa2h-/-/Cgt-/- mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in Fa2h-/-/Cgt-/- mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in Fa2h-/-/Cgt-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h-/-/Cgt-/- mice did not differ significantly from that of Cgt-/- mice, and there was no obvious phenotypic difference between Fa2h-/-/Cgt-/- and Cgt-/- mice Conclusions These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in Cgt-/- mice does not functionally compensate the loss of HFA-GalCer.

  20. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate......Regeneration of myelinated and unmyelinated sensory nerve fibres after a crush lesion of the rat sciatic nerve was investigated by means of retrograde labelling. The advantage of this method is that the degree of regeneration is estimated on the basis of sensory somata rather than the number...... of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion...

  1. Locomotion, physical development, and brain myelination in rats treated with ionizing radiation in utero

    International Nuclear Information System (INIS)

    Zaman, M.S.

    1989-01-01

    Effects of ionizing radiation on the emergence of locomotion skill and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 R, 15 R, and 6.8 R) delivered on the 20th day of the prenatal life. Results indicated that relatively moderate (15 R) to high (150 R) doses of radiation have effects on certain locomotion and physical development parameters. Exposure to 150 R affected pivoting, cliff-avoidance, upper jaw tooth eruption, body weight, and organs, such as brain, cerebral cortex, ovary, kidney, heart and spleen weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption appeared to be affected in the 150 R treated animals. Exposure to 15 R affected pivoting and cliff-avoidance parameters. The cerebral cortex weight of the 15 R treated animals was found to be reduced at the age of day 30. Exposure to 6.8 R had no adverse effects on these parameters. Prenatal exposure to 150 R of radiation reduced the cerebral cortex weight by 22.07% at 30 days of age, and 20.15% at 52 days of age which caused a reduction in cerebral cortex myelin content by 20.16, and 22.89% at the ages of day 30 and day 52 respectively. Exposure to 150 R did not affect the myelin content of the cerebellum or the brain stem; or the myelin concentration (mg myelin/g brain tissue weight) of the cerebral cortex, cerebellum, and the brain stem. Exposure to 15 R, and 6.8 R did not affect either the myelin content or the myelin concentration of these brain areas

  2. Quantification of myelin in children using multiparametric quantitative MRI: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Gi; Choi, Jin Wook [Ajou University School of Medicine, Ajou University Medical Center, Department of Radiology, Suwon (Korea, Republic of); Moon, Won-Jin [Konkuk University Hospital, Konkuk University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, JinJoo [Ajou University School of Medicine, Office of Biostatistics, Department of Humanities and Social Medicine, Suwon (Korea, Republic of)

    2017-10-15

    The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R{sup 2} = 74.6%), middle cerebeller peduncle (R{sup 2} = 76.4%), putamen (R{sup 2} = 95.8%), and centrum semiovale (R{sup 2} = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R{sup 2} = 79.7-93.6%), thalamus (R{sup 2} = 81.7%), and frontal, parietal, temporal, and occipital white matter (R{sup 2} = 92.5-96.5%). Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation. (orig.)

  3. Quantification of myelin in children using multiparametric quantitative MRI: a pilot study

    International Nuclear Information System (INIS)

    Kim, Hyun Gi; Choi, Jin Wook; Moon, Won-Jin; Han, JinJoo

    2017-01-01

    The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R"2 = 74.6%), middle cerebeller peduncle (R"2 = 76.4%), putamen (R"2 = 95.8%), and centrum semiovale (R"2 = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R"2 = 79.7-93.6%), thalamus (R"2 = 81.7%), and frontal, parietal, temporal, and occipital white matter (R"2 = 92.5-96.5%). Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation. (orig.)

  4. Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering

    International Nuclear Information System (INIS)

    De Felici, M; Felici, R; Ferrero, C; Tartari, A; Gambaccini, M; Finet, S

    2008-01-01

    Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

  5. Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation

    Directory of Open Access Journals (Sweden)

    Wang Feng-Chao

    2010-10-01

    Full Text Available Abstract Background Transplantation of oligodendrocyte precursor cells (OPCs is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. Results We transplanted green fluorescent protein (GFP expressed OPCs (GFP-OPCs into injured spinal cords of rats treated with or without CsA (10 mg/kg. Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI. Conclusions These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

  6. Prenatal hydronephrosis: postnatal evaluation and management.

    Science.gov (United States)

    Vemulakonda, Vijaya; Yiee, Jenny; Wilcox, Duncan T

    2014-08-01

    Congenital hydronephrosis is one of the most common anomalies identified on antenatal ultrasound. The underlying etiology of congenital hydronephrosis is multifold, ranging from transient hydronephrosis in utero to clinically significant congenital anomalies of the kidney and urinary tract. While traditional management of hydronephrosis was aimed at relieving symptoms, the advent of routine prenatal ultrasound has led to a shift in the goal of treatment to prevention of renal injury in the asymptomatic patient. However, despite this focus on renal preservation, the diagnostic criteria for identification of children "at risk" for renal damage that can be alleviated by surgical treatment remain a subject of debate. Both antenatal and postnatal imaging studies have been evaluated as indicators for potential reversible renal damage and have been used as potential indicators of the need for surgical intervention. The aim of this review is to discuss the current literature regarding the role of postnatal clinical and radiographic evaluation to identify children who may benefit from early surgical intervention.

  7. Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves

    International Nuclear Information System (INIS)

    Vargas, V.; Vargas, R.; Marquez, G.; Vonasek, E.; Mateu, L.; Luzzati, V.; Borges, J.

    2000-01-01

    Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths. (orig.)

  8. EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

    Science.gov (United States)

    Koprivica, Vuk; Cho, Kin-Sang; Park, Jong Bae; Yiu, Glenn; Atwal, Jasvinder; Gore, Bryan; Kim, Jieun A.; Lin, Estelle; Tessier-Lavigne, Marc; Chen, Dong Feng; He, Zhigang

    2005-10-01

    Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

  9. Radiology of postnatal skeletal development. Pt. 7

    Energy Technology Data Exchange (ETDEWEB)

    Ogden, J.A.; Phillips, S.B.

    1983-02-01

    Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence.

  10. Factors that affecting mothers’ postnatal comfort

    Directory of Open Access Journals (Sweden)

    Gül Pınar

    2009-01-01

    Full Text Available Aim: The comfort is defined as; “an expected result of a complex conformation of providing peace and help about individual’s needs in a physical, psycho-spiritual, social and environmental entity to overcome the problems”. The aim of this study was to determine the mother’s postnatal comfort and the affecting factors of it.Materials and Methods: This is a sectional and descriptive study. The study was performed on the mothers (n=150 who applied to the delivery service of the Başkent University Ankara Hospital between the date of 30.07.2008 to 31.12.2008. A questionnaire was developed by the investigators to collect data and determine patients’ postnatal comfort scores. Results: The mean age of women was 26.4±3.5 years, the majority of patients had an educational level of high school (68.7% and were multipara (66.0%. It was determined that the mothers had problems and needed help with the fatigue, pain, in standing up, the adverse effect of anesthesia, personal and perineal hygiene that affect their postnatal comfort. The comfort score of the mothers who had spontaneous vaginal birth was higher than those of underwent cesarean delivery (p<0.05.Conclusion: The mothers’ needs and expectations about themselves and their babies were generally supplied by midwifes and the nurses in the postnatal period. Opinion of the mothers about their comfort were influenced to a positive view and the comfort scores increased while the mothers’ satisfaction were augmented (p<0.05.

  11. Prenatal and Postnatal Management of Hydronephrosis

    Science.gov (United States)

    Rao, Pravin K.; Palmer, Jeffrey S.

    2009-01-01

    The majority of pregnant women in the U.S. undergo prenatal ultrasonography and approximately 0.5% of these examinations will detect fetal malformations. Up to one-half of these abnormalities include the genitourinary system and the most common urological finding is hydronephrosis. Some conditions associated with prenatal hydronephrosis portend a poor prognosis, while others can follow a fairly benign course. This review focuses on the definition and prenatal assessment of hydronephrosis, fetal intervention, and postnatal management. PMID:19618087

  12. Thyroid hormone action in postnatal heart development

    Directory of Open Access Journals (Sweden)

    Ming Li

    2014-11-01

    Full Text Available Thyroid hormone is a critical regulator of cardiac growth and development, both in fetal life and postnatally. Here we review the role of thyroid hormone in postnatal cardiac development, given recent insights into its role in stimulating a burst of cardiomyocyte proliferation in the murine heart in preadolescence; a response required to meet the massive increase in circulatory demand predicated by an almost quadrupling of body weight during a period of about 21 days from birth to adolescence. Importantly, thyroid hormone metabolism is altered by chronic diseases, such as heart failure and ischemic heart disease, as well as in very sick children requiring surgery for congenital heart diseases, which results in low T3 syndrome that impairs cardiovascular function and is associated with a poor prognosis. Therapy with T3 or thyroid hormone analogs has been shown to improve cardiac contractility; however, the mechanism is as yet unknown. Given the postnatal cardiomyocyte mitogenic potential of T3, its ability to enhance cardiac function by promoting cardiomyocyte proliferation warrants further consideration.

  13. Postnatal development of the endbulb of Held in congenitally deaf cats

    Directory of Open Access Journals (Sweden)

    Christa A Baker

    2010-05-01

    Full Text Available The endbulbs of Held are formed by the ascending branches of myelinated auditory nerve fibers and represent one of the largest synaptic endings in the brain. Normally, these endings are highly branched and each can form up to 1000 dome-shaped synapses. The deaf white cat is a model of congenital deafness involving a type of cochleosaccular degeneration that mimics the Scheibe deformity in humans. Mature deaf white cats exhibit reduced endbulb branching, hypertrophy of postsynaptic densities (PSDs, and changes in synaptic vesicle density. Because cats are essentially deaf at birth, we wanted to determine if the progression of brain abnormalities was linked in time to the failure of normal hearing development. The rationale was that the lack of sound-evoked activity would trigger pathologic change in deaf kittens. The cochleae of deaf cats did not exhibit abnormal morphology at birth. After the first postnatal week, however, the presence of a collapsed scala media signaled the difference between deaf and hearing cats. By working backwards in age, endbulbs of deaf cats expressed flattened and elongated PSDs and increased synaptic vesicle density as compared to normal endbulbs. These differences are present at birth in some white kittens, presaging deafness despite their normal cochlear histology. We speculate that hearing pathology is signaled by a perinatal loss of spontaneous bursting activity in auditory nerve fibers or perhaps by some factor released by hair cell synapses before obliteration of the organ of Corti.

  14. Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nona, S.N.; Stafford, C.A.; Cronly-Dillon, J.R. (Manchester Univ. (United Kingdom). Inst. of Science and Technology); Duncan, A. (Guy' s Hospital, London (United Kingdom). Dept. of Anatomy); Scholes, J. (University Coll., London (United Kingdom))

    1994-07-01

    In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated form the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24 h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. (Author).

  15. Could myelin damage from radiofrequency electromagnetic field exposure help explain the functional impairment electrohypersensitivity? A review of the evidence.

    Science.gov (United States)

    Redmayne, Mary; Johansson, Olle

    2014-01-01

    Myelin provides the electrical insulation for the central and peripheral nervous system and develops rapidly in the first years of life, but continues into mid-life or later. Myelin integrity is vital to healthy nervous system development and functioning. This review outlines the development of myelin through life, and then considers the evidence for an association between myelin integrity and exposure to low-intensity radiofrequency electromagnetic fields (RF-EMFs) typical in the modern world. In RF-EMF peer-reviewed literature examining relevant impacts such as myelin sheath, multiple sclerosis, and other myelin-related diseases, cellular examination was included. There are surprisingly little data available in each area, but considered together a picture begins to emerge in RF-EMF-exposed cases: (1) significant morphological lesions in the myelin sheath of rats; (2) a greater risk of multiple sclerosis in a study subgroup; (3) effects in proteins related to myelin production; and (4) physical symptoms in individuals with functional impairment electrohypersensitivity, many of which are the same as if myelin were affected by RF-EMF exposure, giving rise to symptoms of demyelination. In the latter, there are exceptions; headache is common only in electrohypersensitivity, while ataxia is typical of demyelination but infrequently found in the former group. Overall, evidence from in vivo and in vitro and epidemiological studies suggests an association between RF-EMF exposure and either myelin deterioration or a direct impact on neuronal conduction, which may account for many electrohypersensitivity symptoms. The most vulnerable are likely to be those in utero through to at least mid-teen years, as well as ill and elderly individuals.

  16. Postnatal depression and socio-cultural practices among postnatal mothers in Kota Bahru, Kelantan, Malaysia.

    Science.gov (United States)

    Azidah, A K; Shaiful, B I; Rusli, N; Jamil, M Y

    2006-03-01

    This is a cross sectional study to determine the relationship of postnatal depression (PND) and socio-cultural practices post-delivery among women in Kota Bharu, Kelantan. Four hundred and twenty one pregnant women were screened for depression between 36 - 42 weeks of pregnancy, 1 week and 4 - 6 weeks postpartum using Edinburgh Postnatal Depression Scale (EPDS). The women also completed questionnaires on socio-demography, psychosocial support and traditional postnatal care. The prevalence of PND at 4-6 weeks postpartum was 20.7%. Depressive symptoms at the end of pregnancy (p<0.05) and one week postpartum (p<0.05), worry about the baby (p<0.05), use of traditional medication (p<0.05) and traditional massage (p<0.05) were significantly associated with PND.

  17. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion...

  18. Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects.

    Science.gov (United States)

    Mancini, Matteo; Giulietti, Giovanni; Dowell, Nicholas; Spanò, Barbara; Harrison, Neil; Bozzali, Marco; Cercignani, Mara

    2017-09-14

    Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach. Copyright © 2017. Published by Elsevier Inc.

  19. p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy

    DEFF Research Database (Denmark)

    Song, Yun Ju C; Lundvig, Ditte M S; Huang, Yue

    2007-01-01

    cytoplasmic inclusions. Overall, the data indicate that changes in the cellular interactions between MBP and p25alpha occur early in MSA and contribute to abnormalities in myelin and subsequent alpha-synuclein aggregation and the ensuing neuronal degeneration that characterizes this disease....

  20. Changes in the anisotropy of oriented membrane dynamics induced by myelin basic protein

    Energy Technology Data Exchange (ETDEWEB)

    Natali, F. [OGG-INFM, Grenoble (France); Gliozzi, A.; Rolandi, R.; Relini, A. [Dipartimento di Fisica and Istituto Nazionale per la Fisica della Materia, Universita di Genova (Italy); Cavatorta, P.; Deriu, A. [Dipartimento di Fisica and Istituto Nazionale per la Fisica della Materia, Universita di Parma (Italy); Fasano, A. [Dipartimento di Biochimica e Biologia Molecolare, Universita di Bari (Italy); Riccio, P. [Dipartimento di Biologia D.B.A.F., Universita della Basilicata, Potenza (Italy)

    2002-07-01

    We report recent results showing the evidence of the effect induced by physiological amounts of myelin basic protein (MBP) on the dynamics of dimyristoyl L-a-phosphatidic acid (DMPA) membranes. Incoherent elastic neutron scattering scans, performed over a wide temperature range, have shown that the anisotropy of motions in oriented membranes is significantly enhanced by the presence of MBP. (orig.)

  1. Myelination Is Associated with Processing Speed in Early Childhood: Preliminary Insights.

    Directory of Open Access Journals (Sweden)

    Nicolas Chevalier

    Full Text Available Processing speed is an important contributor to working memory performance and fluid intelligence in young children. Myelinated white matter plays a central role in brain messaging, and likely mediates processing speed, but little is known about the relationship between myelination and processing speed in young children. In the present study, processing speed was measured through inspection times, and myelin volume fraction (VFM was quantified using a multicomponent magnetic resonance imaging (MRI approach in 2- to 5-years of age. Both inspection times and VFM were found to increase with age. Greater VFM in the right and left occipital lobes, the body of the corpus callosum, and the right cerebellum was significantly associated with shorter inspection times, after controlling for age. A hierarchical regression showed that VFM in the left occipital lobe predicted inspection times over and beyond the effects of age and the VFM in the other brain regions. These findings are consistent with the hypothesis that myelin supports processing speed in early childhood.

  2. Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Fenger, Christina

    2009-01-01

    Acute multiple sclerosis lesions are characterized by accumulation of T cells and macrophages, destruction of myelin and oligodendrocytes, and axonal damage. There is, however, limited information on neuroimmune interactions distal to sites of axonal damage in the T cell-infiltrated central nervo...

  3. The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells.

    Science.gov (United States)

    Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

    2017-06-01

    Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.

  4. Ribosomal trafficking is reduced in Schwann cells following induction of myelination

    Directory of Open Access Journals (Sweden)

    James M. Love

    2015-08-01

    Full Text Available Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP in cultured primary rat Schwann cells. This enabled the generation of high-resolution, quantitative data on ribosomal distributions and trafficking dynamics within Schwann cells during early stages of myelination, induced by ascorbic acid treatment. Ribosomes were distributed throughout Schwann cell projections, with ~2-3 bright clusters along each projection. Clusters emerged within 1 day of culture and were maintained throughout early stages of myelination. Three days after induction of myelination, net ribosomal movement remained anterograde (directed away from the Schwann cell body, but ribosomal velocity decreased to about half the levels of the untreated group. Statistical and modeling analysis provided additional insight into key factors underlying ribosomal trafficking. Multiple regression analysis indicated that net transport at early time points was dependent on anterograde velocity, but shifted to dependence on anterograde duration at later time points. A simple, data-driven rate kinetics model suggested that the observed decrease in net ribosomal movement was primarily dictated by an increased conversion of anterograde particles to stationary particles, rather than changes in other directional parameters. These results reveal the strength of a combined experimental and theoretical approach in examining protein localization and transport, and provide evidence of an early establishment of ribosomal populations within Schwann cell projections with a reduction in trafficking following

  5. Psychosocial factors associated with paternal postnatal depression.

    Science.gov (United States)

    Demontigny, Francine; Girard, Marie-Eve; Lacharité, Carl; Dubeau, Diane; Devault, Annie

    2013-08-15

    While maternal postpartum depression is a well-known phenomenon, paternal postnatal depression has been less studied. It is known that paternal postnatal depression impacts on children's and families' development, affects marital satisfaction and affects the economic health of industrialized countries. The aim of this study was to identify the psychosocial factors associated with paternal postnatal depression. A descriptive-correlational study was conducted with a sample of fathers of infants (average age: 11 months) who were breastfed exclusively or predominantly for at least 6 months, comparing psychosocial factors in fathers with (n: 17, 8.2%) and without a positive score for depression on the EPDS scale (n: 188). Psychosocial factors were assessed through questionnaires. Depression in fathers of breastfed infants is associated with the experience of perinatal loss in a previous pregnancy, parenting distress, infant temperament (difficult child), dysfunctional interactions with the child, decreased marital adjustment and perceived low parenting efficacy. Multivariate analysis suggests an independent effect of psychosocial factors such as parenting distress, quality of the marital relationship and perceived parenting efficacy on paternal depression. The sample focused on fathers of breastfed infant, since breastfeeding has become the feeding norm, and this should be taken into account when considering the generalization of findings. These findings emphasize the need to consider a set of psychosocial factors when examining fathers' mental health in the first year of a child's birth. Health professionals can enhance parenting efficacy and alleviate parenting distress by supporting fathers' unique experiences and addressing their needs. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Toll-Like Receptors 2 and 3 Agonists Differentially Affect Oligodendrocyte Survival, Differentiation, and Myelin Membrane Formation

    NARCIS (Netherlands)

    Bsibsi, Malika; Nomden, Anita; van Noort, Johannes M.; Baron, Wia

    Toll-like receptors (TLRs) play a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules as well as endogenous signals. In addition, TLR expression within nonimmune cells has been recognized as as modulator of cell behavior. In this study we have addressed

  7. Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum

    Directory of Open Access Journals (Sweden)

    Nikola Stikov

    2015-09-01

    Full Text Available We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio, as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015.

  8. Early detection and treatment of postnatal depression in primary care.

    Science.gov (United States)

    Davies, Bronwen R; Howells, Sarah; Jenkins, Meryl

    2003-11-01

    Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered 'listening visits' as a first-line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first-line intervention and onward referral can be developed at practitioner level through close collaborative working.

  9. Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.

    Science.gov (United States)

    Karim, Hawra; Kim, Sung Hoon; Lapato, Andrew S; Yasui, Norio; Katzenellenbogen, John A; Tiwari-Woodruff, Seema K

    2018-06-12

    Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis. Copyright © 2018 the Author(s). Published by PNAS.

  10. A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.

    Science.gov (United States)

    Werner, Hauke B; Krämer-Albers, Eva-Maria; Strenzke, Nicola; Saher, Gesine; Tenzer, Stefan; Ohno-Iwashita, Yoshiko; De Monasterio-Schrader, Patricia; Möbius, Wiebke; Moser, Tobias; Griffiths, Ian R; Nave, Klaus-Armin

    2013-04-01

    The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. Copyright © 2013 Wiley Periodicals, Inc.

  11. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    Science.gov (United States)

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  12. Anxiety disorders in pregnancy and the postnatal period ...

    African Journals Online (AJOL)

    Anxiety disorders in pregnancy and the postnatal period. ... Continuing Medical Education ... There is a growing realisation that many women suffer from either new onset or worsening of existing anxiety disorders during pregnancy and postnatally (the perinatal period).1 The occurrence of an anxiety disorder during this time ...

  13. Home births and postnatal practices in madagali, North.Eastern ...

    African Journals Online (AJOL)

    Background: Home births are common in resource poor countries and postnatal practices vary from one community to the other. Objective: To determine the proportion of home births, reasons for home delivery, and evaluate postnatal practices in Madagali, north.eastern Nigeria. Materials and Methods: This was a ...

  14. Barriers to postnatal care and exclusive breastfeeding among ...

    African Journals Online (AJOL)

    Conclusion: Poor knowledge and inaccessibility to health facilities were the main obstacles to postnatal care while the practice of exclusive breastfeeding was limited by the stress and mothers refusal. Keywords: Exclusive breastfeeding, postnatal care, southeastern Nigeria, urban women. Nigerian Medical Journal | Vol.

  15. Validation of the Edinburgh Postnatal Depression Scale on a cohort ...

    African Journals Online (AJOL)

    Posmatal depression occurs in 10 - 15% of women. The Edinburgh Postnatal Depression Scale (EPDS) is a ID-item self-report scale designed specifically as a screening instrument for the postnatal period. It was initially validated for use in the UK, but has subsequently been validated for other communities. It has not been ...

  16. Postnatal corticosteroids and risk of retinopathy of prematurity.

    Science.gov (United States)

    Movsas, Tammy Z; Spitzer, Alan R; Gewolb, Ira H

    2016-08-01

    To investigate the association between postnatal steroids and retinopathy of prematurity (ROP) in neonates born with birth weights at the limit of viability (large study cohort of critically low birth weight infants ROP was more common in neonates exposed to postnatal steroids. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  17. Gemfibrozil, a lipid-lowering drug, increases myelin genes in human oligodendrocytes via peroxisome proliferator-activated receptor-β.

    Science.gov (United States)

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J; Pahan, Kalipada

    2012-10-05

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(-/-) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(-/-) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases.

  18. Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β*

    Science.gov (United States)

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J.; Pahan, Kalipada

    2012-01-01

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(−/−) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(−/−) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases. PMID:22879602

  19. The dwelling space of postnatal care.

    Science.gov (United States)

    Smythe, Elizabeth A; Payne, Deborah; Wilson, Sally; Wynyard, Sue

    2013-06-01

    This paper considers the dwelling space of postnatal care, how being-there feels for the woman going through the experience of matrescence. The research takes a hermeneutic approach and draws on philosophical notions from Heidegger. 'What is the nature of the dwelling space of valued postnatal care?'. Appropriate ethics approval was gained. Participants were midwives, nurses, women, and other relevant stakeholders. There were 4 focus groups involving 11 participants and 19 individual interviews. Data collection was conducted over a one week period by a team of three researchers. An interview schedule had been organised by the administrator at the Centre. Participants chose whether to come to the centre to be interviewed, or be interviewed in their own homes. Most interviews were an hour. All interviews were tape recorded and transcribed, with the participant's permission. Data was analysed through a hermeneutic process set in the context of related literature. When women are invited into a dwelling space that strengthens them they feel 'mothered': being listened to, have their needs anticipated, and are cared for in a loving manner. In such a way they grow confidence. A child health nurse reported the difference such care made to on-going mothering at home. All women deserve a dwelling space in their early days of matrescence. Small birthing centres perhaps achieve such care and ambience more easily than large institutional units. Nevertheless, wherever the place, practices need to be enabled that foster the spirit of dwelling. Copyright © 2012 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  20. Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

    International Nuclear Information System (INIS)

    Zhang Lei; Hao Changchun; Feng Ying; Gao Feng; Lu Xiaolong; Li Junhua; Sun Runguang

    2016-01-01

    Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure–area ( π – A ) and pressure–time ( π – T ) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. (special topic)

  1. Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Biggins, J.A.; Taylor, A.; Caspary, E.A.

    1978-01-01

    Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

  2. A New Method for Automated Identification and Morphometry of Myelinated Fibers Through Light Microscopy Image Analysis

    OpenAIRE

    Novas, Romulo Bourget; Fazan, Valeria Paula Sassoli; Felipe, Joaquim Cezar

    2015-01-01

    Nerve morphometry is known to produce relevant information for the evaluation of several phenomena, such as nerve repair, regeneration, implant, transplant, aging, and different human neuropathies. Manual morphometry is laborious, tedious, time consuming, and subject to many sources of error. Therefore, in this paper, we propose a new method for the automated morphometry of myelinated fibers in cross-section light microscopy images. Images from the recurrent laryngeal nerve of adult rats and ...

  3. MAL Overexpression Leads to Disturbed Expression of Genes That Influence Cytoskeletal Organization and Differentiation of Schwann Cells

    Directory of Open Access Journals (Sweden)

    Daniela Schmid

    2014-09-01

    Full Text Available In the developing peripheral nervous system, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate myelination. The myelin and lymphocyte protein MAL is a component of lipid rafts that is important for targeting proteins and lipids to distinct domains. MAL overexpression impedes peripheral myelinogenesis, which is evident by a delayed onset of myelination and reduced expression of the myelin protein zero (Mpz/P0 and the low-affinity neurotrophin receptor p75NTR . This study shows that MAL overexpression leads to a significant reduction of Mpz and p75NTR expression in primary mouse Schwann cell cultures, which was already evident before differentiation, implicating an effect of MAL in early Schwann cell development. Their transcription was robustly reduced, despite normal expression of essential transcription factors and receptors. Further, the cAMP response element-binding protein (CREB and phosphoinositide 3-kinase signaling pathways important for Schwann cell differentiation were correctly induced, highlighting that other so far unknown rate limiting factors do exist. We identified novel genes expressed by Schwann cells in a MAL-dependent manner in vivo and in vitro. A number of those, including S100a4, RhoU and Krt23, are implicated in cytoskeletal organization and plasma membrane dynamics. We showed that S100a4 is predominantly expressed by nonmyelinating Schwann cells, whereas RhoU was localized within myelin membranes, and Krt23 was detected in nonmyelinating as well as in myelinating Schwann cells. Their differential expression during early peripheral nerve development further underlines their possible role in influencing Schwann cell differentiation and myelination.

  4. A qualitative study of the acceptability of routine screening of postnatal women using the Edinburgh Postnatal Depression Scale.

    Science.gov (United States)

    Shakespeare, Judy; Blake, Fiona; Garcia, Jo

    2003-01-01

    BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) has been widely recommended and implemented in primary care, although little is known about how acceptable it is to women. AIM: To explore the acceptability to women of postnatal screening by health visitors with the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal patients from 22 general practices within the area of Oxford City Primary Care Group. METHOD: Thirty-nine postnatal women from a purposive sample were interviewed, chosen on the basis of different general practices, EPDS results at eight weeks and eight months postnatal, and whether 'listening visits' were received. The interviews were analysed using the constant comparative method. RESULTS: Just over half of the women interviewed found screening with the EPDS less than acceptable, whatever their postnatal emotional health. The main themes identified were problems with the process of screening and, in particular, the venue, the personal intrusion of screening and stigma. The women interviewed had a clear preference for talking about how they felt, rather than filling out a questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was less than acceptable for the majority of women. This is of concern, as universal screening with the EPDS for the detection of postnatal depression is already recommended and widespread in primary care. PMID:14601337

  5. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

    Science.gov (United States)

    Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

    2008-12-15

    A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

  6. Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins

    Science.gov (United States)

    Barker, Rachel; Wellington, Dannielle; Esiri, Margaret M; Love, Seth

    2013-01-01

    White matter ischemia is difficult to quantify histologically. Myelin-associated glycoprotein (MAG) is highly susceptible to ischemia, being expressed only adaxonally, far from the oligodendrocyte cell body. Myelin-basic protein (MBP) and proteolipid protein (PLP) are expressed throughout the myelin sheath. We compared MAG, MBP, and PLP levels in parietal white matter homogenates from 17 vascular dementia (VaD), 49 Alzheimer's disease (AD), and 33 control brains, after assessing the post-mortem stability of these proteins. Small vessel disease (SVD) and cerebral amyloid angiopathy (CAA) severity had been assessed in paraffin sections. The concentration of MAG remained stable post-mortem, declined with increasing SVD, and was significantly lower in VaD than controls. The concentration of MBP fell progressively post-mortem, limiting its diagnostic utility in this context. Proteolipid protein was stable post-mortem and increased significantly with SVD severity. The MAG/PLP ratio declined significantly with SVD and CAA severity. The MAG and PLP levels and MAG/PLP did not differ significantly between AD and control brains. We validated the utility of MAG and MAG/PLP measurements on analysis of 74 frontal white matter samples from an Oxford cohort in which SVD had previously been scored. MAG concentration and the MAG/PLP ratio are useful post-mortem measures of ante-mortem white matter ischemia. PMID:23532085

  7. Histological methods for assessing myelin sheaths and axons in human nerve trunks.

    Science.gov (United States)

    Miko, T L; Gschmeissner, S E

    1994-03-01

    Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods.

  8. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

    Directory of Open Access Journals (Sweden)

    Terry B Huff

    2011-03-01

    Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  9. Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves

    International Nuclear Information System (INIS)

    ElBarrany, Wagih G.; Hamdy, Raid M.; AlHayani, Abdulmonem A.; Jalalah, Sawsan M.

    2009-01-01

    To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

  10. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana; Pinchenko, Volodymyr

    2011-01-01

    Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and prog......Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe...... and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which...... is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies...

  11. Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content.

    Science.gov (United States)

    Bouhrara, Mustapha; Reiter, David A; Bergeron, Christopher M; Zukley, Linda M; Ferrucci, Luigi; Resnick, Susan M; Spencer, Richard G

    2018-04-18

    We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using magnetic resonance imaging of myelin. Brains of young and old controls and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging-based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, relationship of functional status to myelination status, and therapeutics. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials. Copyright © 2018. Published by Elsevier Inc.

  12. Postnatal brain and skull growth in an Apert syndrome mouse model

    Science.gov (United States)

    Hill, Cheryl A.; Martínez-Abadías, Neus; Motch, Susan M.; Austin, Jordan R.; Wang, Yingli; Jabs, Ethylin Wang; Richtsmeier, Joan T.; Aldridge, Kristina

    2012-01-01

    Craniofacial and neural tissues develop in concert throughout pre- and postnatal growth. FGFR-related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for Apert syndrome using the Fgfr2+/P253R mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three-dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2+/P253R mice and unaffected littermates at P0 (N=28) and P2 (N=23). 3D coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull-brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. PMID:23495236

  13. Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.

    Science.gov (United States)

    Manogaran, Praveena; Vavasour, Irene M; Lange, Alex P; Zhao, Yinshan; McMullen, Katrina; Rauscher, Alexander; Carruthers, Robert; Li, David K B; Traboulsee, Anthony L; Kolind, Shannon H

    2016-01-01

    The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury. To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls. 12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density. Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm(3), SD = 0.06) compared to those without (mean = 0.97 mm(3), SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent

  14. Challenges in the prenatal and post-natal diagnosis of mediastinal cystic hygroma: a case report

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    Nazir Sarfraz

    2008-08-01

    Full Text Available Abstract Introduction Cystic hygroma is a benign congenital neoplasm that mostly presents as a soft-tissue mass in the posterior triangle of the neck. Pure mediastinal lesions are uncommon; the vast majority are asymptomatic and are an incidental finding in adulthood. The diagnosis is often made intra- or postoperatively. Prenatal identification is exceptional and post-natal diagnosis also proves challenging. Case presentation We report one such case that was mistaken for other entities in both the prenatal and immediate post-natal period. Initial and follow-up antenatal ultrasound scans demonstrated a multicystic lesion in the left chest, and the mother was counselled about the possibility of her baby having a congenital diaphragmatic hernia. Initial post-natal chest radiographs were reported as normal. An echocardiogram and thoracic computed tomography scan confirmed a complex multiloculated cystic mediastinal mass. The working diagnoses were of a mediastinal teratoma or congenital cystic adenomatous malformation. At operation, the lesion was compressed by the left lung and was found to be close to the left phrenic nerve, which was carefully identified and preserved. After excision, histopathological examination of the mass confirmed the diagnosis of cystic hygroma. Postoperative dyspnoea was observed secondary to paradoxical movement of the left hemidiaphragm and probable left phrenic neuropraxia. This settled conservatively with excellent recovery. Conclusion Despite the fact that isolated intrathoracic cystic hygroma is a rare entity, it needs to be considered in the differential diagnosis of foetal and neonatal mediastinal masses, particularly for juxtadiaphragmatic lesions. The phrenic nerve is not identifiable on prenatal ultrasound imaging, and it is therefore understandable that a mass close to the diaphragm may be mistaken for a congenital diaphragmatic hernia because of the location, morphology and potential phrenic nerve compression

  15. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

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    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  16. A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

    Science.gov (United States)

    Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

    2018-01-19

    OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

  17. Integrative Temporo-Spatial, Mineralogic, Spectroscopic, and Proteomic Analysis of Postnatal Enamel Development in Teeth with Limited Growth

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    Mirali Pandya

    2017-10-01

    Full Text Available Tooth amelogenesis is a complex process beginning with enamel organ cell differentiation and enamel matrix secretion, transitioning through changes in ameloblast polarity, cytoskeletal, and matrix organization, that affects crucial biomineralization events such as mineral nucleation, enamel crystal growth, and enamel prism organization. Here we have harvested the enamel organ including the pliable enamel matrix of postnatal first mandibular mouse molars during the first 8 days of tooth enamel development to conduct a step-wise cross-sectional analysis of the changes in the mineral and protein phase. Mineral phase diffraction pattern analysis using single-crystal, powder sample X-ray diffraction analysis indicated conversion of calcium phosphate precursors to partially fluoride substituted hydroxyapatite from postnatal day 4 (4 dpn onwards. Attenuated total reflectance spectra (ATR revealed a substantial elevation in phosphate and carbonate incorporation as well as structural reconfiguration between postnatal days 6 and 8. Nanoscale liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS demonstrated highest protein counts for ECM/cell surface proteins, stress/heat shock proteins, and alkaline phosphatase on postnatal day 2, high counts for ameloblast cytoskeletal proteins such as tubulin β5, tropomyosin, β-actin, and vimentin on postnatal day 4, and elevated levels of cofilin-1, calmodulin, and peptidyl-prolyl cis-trans isomerase on day 6. Western blot analysis of hydrophobic enamel proteins illustrated continuously increasing amelogenin levels from 1 dpn until 8 dpn, while enamelin peaked on days 1 and 2 dpn, and ameloblastin on days 1–5 dpn. In summary, these data document the substantial changes in the enamel matrix protein and mineral phase that take place during postnatal mouse molar amelogenesis from a systems biological perspective, including (i relatively high levels of matrix protein expression during the early

  18. PHYSIOTHERAPY EXERCISES DURING ANTENATAL AND POSTNATAL

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    Hannah Rajsekhar

    2015-10-01

    Full Text Available Background: It’s a well-known fact that exercise is good for the mind and body making it beneficial for expectant and new mothers. The challenge of pregnancy, labor and looking after a new born is not an easy task. So the fitter you are the better you will cope with this life changing event. Method: Aerobic and strengthening exercises help in adjusting to the increasing weight and posture changes to cope effectively with the labor and the postnatal period. Although exercises in pregnancy are extremely beneficial, they can cause more harm than good if not done correctly. Medical screening for exercise should be done by the Doctor as well as the Physiotherapist to ensure that the patient underwent a basic screening, assessment or continued monitoring for the right exercise protocol for avoidance of any complications and to ensure the benefits of staying healthy and fit. Results: Evidence shows that exercise training programs designed and delivered by the Physiotherapists can relieve the prenatal post natal problems. Conclusion: Number of studies has shown the positive effects of aerobic and strengthening exercises on pregnant women. The physical changes to a pregnant woman’s body are multiple. There are center of mass changes, pressure on the organs and increased weight gain. In fact, over two thirds of pregnant women experience back pain, one fifth experience pelvic pain and over 40% experience urinary incontinence in their first pregnancy.

  19. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  20. Comparative Analyses between Skeletal Muscle miRNAomes from Large White and Min Pigs Revealed MicroRNAs Associated with Postnatal Muscle Hypertrophy.

    Science.gov (United States)

    Sheng, Xihui; Wang, Ligang; Ni, Hemin; Wang, Lixian; Qi, Xiaolong; Xing, Shuhan; Guo, Yong

    2016-01-01

    The molecular mechanism regulated by microRNAs (miRNAs) that underlies postnatal hypertrophy of skeletal muscle is complex and remains unclear. Here, the miRNAomes of longissimus dorsi muscle collected at five postnatal stages (60, 120, 150, 180, and 210 days after birth) from Large White (commercial breed) and Min pigs (indigenous breed of China) were analyzed by Illumina sequencing. We identified 734 miRNAs comprising 308 annotated miRNAs and 426 novel miRNAs, of which 307 could be considered pig-specific. Comparative analysis between two breeds suggested that 60 and 120 days after birth were important stages for skeletal muscle hypertrophy and intramuscular fat accumulation. A total of 263 miRNAs were significantly differentially expressed between two breeds at one or more developmental stages. In addition, the differentially expressed miRNAs between every two adjacent developmental stages in each breed were determined. Notably, ssc-miR-204 was significantly more highly expressed in Min pig skeletal muscle at all postnatal stages compared with its expression in Large White pig skeletal muscle. Based on gene ontology and KEGG pathway analyses of its predicted target genes, we concluded that ssc-miR-204 may exert an impact on postnatal hypertrophy of skeletal muscle by regulating myoblast proliferation. The results of this study will help in elucidating the mechanism underlying postnatal hypertrophy of skeletal muscle modulated by miRNAs, which could provide valuable information for improvement of pork quality and human myopathy.

  1. Postnatal growth, age estimation and development of foraging ...

    Indian Academy of Sciences (India)

    Unknown

    mothers. There was no significant difference in the growth pattern of the young maintained in captivity compared ..... interactions, and development of vocalizations in the vesper- ... Kunz T H and Hood W R 2000 Parental care and postnatal.

  2. Risk factors for antenatal depression, postnatal depression and parenting stress

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    Milgrom Jeannette

    2008-04-01

    Full Text Available Abstract Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161 also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI. Results Regression analyses identified significant risk factors for the three outcome measures. (1. Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2. Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3. Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator

  3. Risk factors for antenatal depression, postnatal depression and parenting stress.

    Science.gov (United States)

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-04-16

    Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for

  4. Prenatal and postnatal depression among low income Brazilian women

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    V.A. Da-Silva

    1998-06-01

    Full Text Available Postnatal depression is a significant problem affecting 10-15% of mothers in many countries and has been the subject of an increasing number of publications. Prenatal depression has been studied less. The aims of the present investigation were: 1 to obtain information on the prevalence of prenatal and postnatal depression in low income Brazilian women by using an instrument already employed in several countries, i.e., the Edinburgh Postnatal Depression Scale (EPDS; 2 to evaluate the risk factors involved in prenatal and postnatal depression in Brazil. The study groups included 33 pregnant women interviewed at home during the second and third trimesters of pregnancy, and once a month during the first six months after delivery. Questions on life events and the mother's relationship with the baby were posed during each visit. Depressed pregnant women received less support from their partners than non-depressed pregnant women (36.4 vs 72.2%, P<0.05; Fisher exact test. Black women predominated among pre- and postnatally depressed subjects. Postnatal depression was associated with lower parity (0.4 ± 0.5 vs 1.1 ± 1.0, P<0.05; Student t-test. Thus, the period of pregnancy may be susceptible to socio-environmental factors that induce depression, such as the lack of affective support from the partner. The prevalence rate of 12% observed for depression in the third month postpartum is comparable to that of studies from other countries.

  5. Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

    Science.gov (United States)

    Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

    2017-12-01

    We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

  6. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    Science.gov (United States)

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Promoting Myelination in an In Vitro Mouse Model of the Peripheral Nerve System: The Effect of Wine Ingredients

    Science.gov (United States)

    Stettner, Mark; Wolffram, Kathleen; Mausberg, Anne K.; Albrecht, Philipp; Derksen, Angelika; Methner, Axel; Dehmel, Thomas; Hartung, Hans-Peter; Dietrich, Helmut; Kieseier, Bernd C.

    2013-01-01

    Protective properties of moderate wine consumption against cancers, cardiovascular, metabolic and degenerative diseases have been reported in various clinical studies. Here, we analysed the effect of red wine (RW) and white wine (WW) on myelination using an in vitro embryonic co-culture mouse model. The total amount of myelin was found to be significantly increased after RW and WW treatment, while only RW significantly increased the number of internodes. Both types of wine increased rat Schwann cell- (rSC) expression of the NAD+-dependent deacetylase sirtuin-two-homolog 2 (Sirt2), a protein known to be involved in myelination. Detailed chemical analysis of RW revealed a broad spectrum of anthocyanins, piceids, and phenolics, including resveratrol (RSV). In our assay system RSV in low concentrations induced myelination. Furthermore RSV raised intracellular glutathione concentrations in rSCs and in co-cultures and therefore augmented antioxidant capacity. We conclude that wine promotes myelination in a rodent in vitro model by controlling intracellular metabolism and SC plasticity. During this process, RSV exhibits protective properties; however, the fostering effect on myelinaton during exposure to wine appears to be a complex interaction of various compounds. PMID:23762469

  8. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

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    Zahir Kizilay

    2016-01-01

    Full Text Available The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7: control (C, boric acid (BA, sciatic nerve injury (I , and sciatic nerve injury + boric acid treatment (BAI. Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

  9. The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes and myelin lipid composition.

    Science.gov (United States)

    Singhal, N K; Huang, H; Li, S; Clements, R; Gadd, J; Daniels, A; Kooijman, E E; Bannerman, P; Burns, T; Guo, F; Pleasure, D; Freeman, E; Shriver, L; McDonough, J

    2017-01-01

    The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L -/- ) mice which do not synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing white matter that mirrored decreased levels of NAA. We also discovered decreases in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L -/- mice compared to controls. Metabolomic analysis of primary cultures of oligodendrocytes treated with NAA revealed increased levels of α-ketoglutarate, which has been reported to regulate histone demethylase activity. Consistent with this, NAA treatment resulted in alterations in the levels of histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3 histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3 has been linked to alterations in transcriptional repression in developing oligodendrocytes. We also noted the NAA treatment was associated with increases in the expression of genes involved in sulfatide and sphingomyelin synthesis in cultured oligodendrocytes. This is the first report demonstrating that neuronal-derived NAA can signal to the oligodendrocyte nucleus. These data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination.

  10. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

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    Han Ruolan

    2008-04-01

    Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

  11. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    Science.gov (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  12. 'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

    Science.gov (United States)

    Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

    2018-04-01

    To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

  13. Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

    Science.gov (United States)

    Zhang, Lei; Hao, Changchun; Feng, Ying; Gao, Feng; Lu, Xiaolong; Li, Junhua; Sun, Runguang

    2016-09-01

    Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure-area (π-A) and pressure-time (π-T) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. Project supported by the National Natural Science Foundation of China (Grant Nos. 21402114 and 11544009), the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2016JM2010), the Fundamental Research Funds for the Central

  14. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

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    Liu Huaqing

    2012-06-01

    Full Text Available Abstract Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia. The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI, are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1

  15. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain.

    Science.gov (United States)

    Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

    2012-06-07

    The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia

  16. Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice.

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    Toufik Taib

    Full Text Available Traumatic brain injury (TBI results in white matter injury (WMI that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i neuroinflammation, (ii WMI and (iii behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model

  17. An αII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration.

    Science.gov (United States)

    Huang, Claire Yu-Mei; Zhang, Chuansheng; Zollinger, Daniel R; Leterrier, Christophe; Rasband, Matthew N

    2017-11-22

    Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αII spectrin-deficient mice of both sexes and found that, in myelinated axons, αII spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αII spectrin disrupts this organization. Avil-cre;Sptan1 f/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K + channels. We show that the density of nodal βIV spectrin is constant among axons, but the density of nodal αII spectrin increases with axon diameter. Remarkably, Avil-cre;Sptan1 f/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αII spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αII spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier. SIGNIFICANCE STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mechanical forces to which they are exposed (e.g., compression, torsion, and stretch). However, until now, no vertebrate animal model has tested the requirement of the spectrin cytoskeleton in

  18. The lactate receptor HCAR1 promotes neuronal development and protects axons and myelin during hypoglycemia

    DEFF Research Database (Denmark)

    Kennedy, L. H.; Andersson, K. A.; Haugen, O. P.

    2017-01-01

    Lactate plays a significant role as an energy supply for neurons and has a neuroprotective effect in hypoglycemia and ischemia (1±5). Further, oligodendrocytes can use lactate for myelination when glucose levels are low. New studies suggest that lactate is not only a metabolic fuel but also...... in the development and survival of neurons and oligodendrocytes in normal conditions and hypoglycemia. We show that young HCAR1 KO mice have a reduced number of neural progenitor cells in the hippocampus and the cerebral cortex, and the average size of cortical axons is smaller in KO compared with WT mice...

  19. The use of Edinburgh Postnatal Depression Scale to identify postnatal depression symptoms at well child visit

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    Silvestri Maria

    2009-10-01

    Full Text Available Abstract Objectives 1 to evaluate the role of the pediatrician in detecting postnatal depression (PD symptoms by the Edinburgh Postnatal Depression Scale (EPDS; 2 to detect factors increasing the risk of PD and, 3 to assess the importance of scores gained from fathers' questionnaire. Methods we surveyed 1122 mothers and 499 fathers who were assessed using the EPDS during the first well-child visit. After 5 weeks, high scoring parents, completed a second EPDS. High scoring parents were examined by a psychiatrist who had to confirm the PD diagnosis. Results 26.6% of mothers and 12.6% of fathers at the first visit, 19.0% of mothers and 9.1% of fathers at the second visit, gained scores signaling the risk of PD. Four mothers and two fathers had confirmed PD diagnosis. Younger maternal age, non-Italian nationality and low socio-economic condition were related to higher EPDS scores. Conclusion PD is common in the average population. Using a simple and standardized instrument, pediatricians are able to detect parents with higher risk of suffering from PD.

  20. Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

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    Xiu-Ming Wu

    Full Text Available Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

  1. Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice.

    Science.gov (United States)

    Zendedel, Adib; Kashani, Iraj Ragerdi; Azimzadeh, Maryam; Pasbakhsh, Parichehr; Omidi, Negar; Golestani, Abolfazl; Beyer, Cordian; Clarner, Tim

    2016-04-01

    Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and remyelination. Triiodothyronin (T3) is thought to enhance remyelination in the adult brain by the induction of oligodendrocyte maturation. We investigated additional astrocyte-mediated mechanisms by which T3 might promote remyelination in chronically demyelinated lesions using the cuprizone mouse model. C57BL/6 mice were fed cuprizone for 12 weeks to induce lesions with an impaired remyelination capacity. While the expression of oligodenrocyte progenitor markers, i.e., platelet derived growth factor-α receptor was not affected by T3 administration, myelination status, myelin protein expression as well as total and adult oligodendrocyte numbers were markedly increased compared to cuprizone treated controls. In addition to these effects on oligodendrocyte numbers and function, astrogliosis but not microgliosis was ameliorated by T3 administration. Intermediate filament proteins vimentin and nestin as well as the extracellular matrix component tenascin C were significantly reduced after T3 exposure, indicating additional effects of T3 on astrocytes and astrogliosis. Our data clearly indicate that T3 promotes remyelination in chronic lesions by both enhancing oligodendrocyte maturation and attenuating astrogliosis.

  2. [Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

    Science.gov (United States)

    Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

    Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

  3. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Falzon, G; Pearson, S; Murison, R; Hall, C; Siu, K; Round, A; Schueltke, E; Kaye, A H; Lewis, R

    2007-01-01

    Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma

  4. Epitope diversity of N-glycans from bovine peripheral myelin glycoprotein P0 revealed by mass spectrometry and nano probe magic angle spinning 1H NMR spectroscopy

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Gutiérrez Gallego, R.; Jiménez Blanco, J.L.; Thijssen-van Zuylen, C.W.E.M.; Gotfredsen, C.H.; Voshol, H.; Duus, J.Ø.; Schachner, M.

    2001-01-01

    The carbohydrate structures present on the glycoproteins in the central and peripheral nerve systems are essential in many cell adhesion processes. The P0 glycoprotein, expressed by myelinating Schwann cells, plays an important role during the formation and maintenance of myelin, and it is the most

  5. Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure

    Directory of Open Access Journals (Sweden)

    Hayashi Nobuhiro

    2008-02-01

    Full Text Available Abstract Background The myelin sheath is a multilamellar membrane structure wrapped around the axon, enabling the saltatory conduction of nerve impulses in vertebrates. Myelin basic protein, one of the most abundant myelin-specific proteins, is an intrinsically disordered protein that has been shown to bind calmodulin. In this study, we focus on a 19-mer synthetic peptide from the predicted calmodulin-binding segment near the C-terminus of human myelin basic protein. Results The interaction of native human myelin basic protein with calmodulin was confirmed by affinity chromatography. The binding of the myelin basic protein peptide to calmodulin was tested with isothermal titration calorimetry (ITC in different temperatures, and Kd was observed to be in the low μM range, as previously observed for full-length myelin basic protein. Surface plasmon resonance showed that the peptide bound to calmodulin, and binding was accompanied by a conformational change; furthermore, gel filtration chromatography indicated a decrease in the hydrodynamic radius of calmodulin in the presence of the peptide. NMR spectroscopy was used to map the binding area to reside mainly within the hydrophobic pocket of the C-terminal lobe of calmodulin. The solution structure obtained by small-angle X-ray scattering indicates binding of the myelin basic protein peptide into the interlobal groove of calmodulin, while calmodulin remains in an extended conformation. Conclusion Taken together, our results give a detailed structural insight into the interaction of calmodulin with a C-terminal segment of a major myelin protein, the myelin basic protein. The used 19-mer peptide interacts mainly with the C-terminal lobe of calmodulin, and a conformational change accompanies binding, suggesting a novel mode of calmodulin-target protein interaction. Calmodulin does not collapse and wrap around the peptide tightly; instead, it remains in an extended conformation in the solution structure

  6. Women's views of postnatal care in the context of the increasing pressure on postnatal beds in Australia.

    Science.gov (United States)

    McLachlan, Helen L; Gold, Lisa; Forster, Della A; Yelland, Jane; Rayner, Joanne; Rayner, Sharon

    2009-12-01

    Despite limited evidence evaluating early postnatal discharge, length of hospital stay has declined dramatically in Australia since the 1980s. The recent rising birth rate in Victoria, Australia has increased pressure on hospital beds, and many services have responded by discharging women earlier than planned, often with little preparation during pregnancy. We aimed to explore the views of women and their partners regarding a number of theoretical postnatal care 'packages' that could provide an alternative approach to early postnatal care. Eight focus groups and four interviews were held in rural and metropolitan Victoria in 2006 with participants who had experienced a mix of public and private maternity care. These included 8 pregnant women, 42 recent mothers and 2 male partners. All were fluent in English. Focus groups explored participants' experiences and/or expectations of early postnatal care in hospital and at home and their views of alternative packages of postnatal care where location of care shifted from hospital to home and/or hotel. This paper describes the packages and explores and describes what 'value' women placed on the various components of care. Overall, women expressed a preference for what they had experienced or expected, which may be explained by the 'what is must be best' phenomenon where women place value on the status quo. They generally did not respond favourably towards the alternative postnatal care packages, with concerns about any shorter length of hospital stay, especially for first time mothers. Women were concerned about the safety and wellbeing of their new baby and reported that they lacked confidence in their ability to care for their baby. The physical presence and availability of professional support was seen to alleviate these concerns, especially for first time mothers. Participants did not believe that increased domiciliary visits compensated for forgoing the perceived security and value of staying in hospital. Women

  7. Postnatal growth standards for preterm infants: the Preterm Postnatal Follow-up Study of the INTERGROWTH-21(st) Project.

    Science.gov (United States)

    Villar, José; Giuliani, Francesca; Bhutta, Zulfiqar A; Bertino, Enrico; Ohuma, Eric O; Ismail, Leila Cheikh; Barros, Fernando C; Altman, Douglas G; Victora, Cesar; Noble, Julia A; Gravett, Michael G; Purwar, Manorama; Pang, Ruyan; Lambert, Ann; Papageorghiou, Aris T; Ochieng, Roseline; Jaffer, Yasmin A; Kennedy, Stephen H

    2015-11-01

    Charts of size at birth are used to assess the postnatal growth of preterm babies on the assumption that extrauterine growth should mimic that in the uterus. The INTERGROWTH-21(st) Project assessed fetal, newborn, and postnatal growth in eight geographically defined populations, in which maternal health care and nutritional needs were met. From these populations, the Fetal Growth Longitudinal Study selected low-risk women starting antenatal care before 14 weeks' gestation and monitored fetal growth by ultrasonography. All preterm births from this cohort were eligible for the Preterm Postnatal Follow-up Study, which included standardised anthropometric measurements, feeding practices based on breastfeeding, and data on morbidity, treatments, and development. To construct the preterm postnatal growth standards, we selected all live singletons born between 26 and before 37 weeks' gestation without congenital malformations, fetal growth restriction, or severe postnatal morbidity. We did analyses with second-degree fractional polynomial regression models in a multilevel framework accounting for repeated measures. Fetal and neonatal data were pooled from study sites and stratified by postmenstrual age. For neonates, boys and girls were assessed separately. From 4607 women enrolled in the study, there were 224 preterm singleton births, of which 201 (90%) were enrolled in the Preterm Postnatal Follow-up Study. Variance component analysis showed that only 0·2% and 4·0% of the total variability in postnatal length and head circumference, respectively, could be attributed to between-site differences, justifying pooling the data from all study sites. Preterm growth patterns differed from those for babies in the INTERGROWTH-21(st) Newborn Size Standards. They overlapped with the WHO Child Growth Standards for term babies by 64 weeks' postmenstrual age. Our data have yielded standards for postnatal growth in preterm infants. These standards should be used for the assessment of

  8. Prenatal and early postnatal stress and later life inflammation

    DEFF Research Database (Denmark)

    Pedersen, Jolene Masters; Mortensen, Erik Lykke; Christensen, Dinne Skjærlund

    2018-01-01

    BACKGROUND: Evidence suggests that maternal psychological and social stress during the prenatal period and in childhood represent an important condition that may adversely impact the anatomy and physiology of the developing child with implications for a number of health-related conditions...... and postnatal stressor data was collected at year one follow-up. A series of ordinary least square regression models were performed with the stress measures as the exposures and C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor necrosis factor α (TNF-α) separately as the outcomes...... in the first year of life, was associated with higher levels of CRP and IL-6. The accumulation of social stressors in the early postnatal period was associated with higher levels of CRP and IL-6 but not IL-10 and TNF-α. The accumulation of stressors in the prenatal and postnatal periods combined was associated...

  9. Long non-coding RNA expression profiling of mouse testis during postnatal development.

    Directory of Open Access Journals (Sweden)

    Jin Sun

    Full Text Available Mammalian testis development and spermatogenesis play critical roles in male fertility and continuation of a species. Previous research into the molecular mechanisms of testis development and spermatogenesis has largely focused on the role of protein-coding genes and small non-coding RNAs, such as microRNAs and piRNAs. Recently, it has become apparent that large numbers of long (>200 nt non-coding RNAs (lncRNAs are transcribed from mammalian genomes and that lncRNAs perform important regulatory functions in various developmental processes. However, the expression of lncRNAs and their biological functions in post-natal testis development remain unknown. In this study, we employed microarray technology to examine lncRNA expression profiles of neonatal (6-day-old and adult (8-week-old mouse testes. We found that 8,265 lncRNAs were expressed above background levels during post-natal testis development, of which 3,025 were differentially expressed. Candidate lncRNAs were identified for further characterization by an integrated examination of genomic context, gene ontology (GO enrichment of their associated protein-coding genes, promoter analysis for epigenetic modification, and evolutionary conservation of elements. Many lncRNAs overlapped or were adjacent to key transcription factors and other genes involved in spermatogenesis, such as Ovol1, Ovol2, Lhx1, Sox3, Sox9, Plzf, c-Kit, Wt1, Sycp2, Prm1 and Prm2. Most differentially expressed lncRNAs exhibited epigenetic modification marks similar to protein-coding genes and tend to be expressed in a tissue-specific manner. In addition, the majority of differentially expressed lncRNAs harbored evolutionary conserved elements. Taken together, our findings represent the first systematic investigation of lncRNA expression in the mammalian testis and provide a solid foundation for further research into the molecular mechanisms of lncRNAs function in mammalian testis development and spermatogenesis.

  10. Early postnatal development of electrophysiological and histological properties of sensory sural nerves in male rats that were maternally deprived and artificially reared: Role of tactile stimulation.

    Science.gov (United States)

    Zempoalteca, Rene; Porras, Mercedes G; Moreno-Pérez, Suelem; Ramirez-Funez, Gabriela; Aguirre-Benítez, Elsa L; González Del Pliego, Margarita; Mariscal-Tovar, Silvia; Mendoza-Garrido, Maria E; Hoffman, Kurt Leroy; Jiménez-Estrada, Ismael; Melo, Angel I

    2018-04-01

    Early adverse experiences disrupt brain development and behavior, but little is known about how such experiences impact on the development of the peripheral nervous system. Recently, we found alterations in the electrophysiological and histological characteristics of the sensory sural (SU) nerve in maternally deprived, artificially reared (AR) adult male rats, as compared with maternally reared (MR) control rats. In the present study, our aim was to characterize the ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were (1) AR group, (2) AR and received daily tactile stimulation to the body and anogenital region (AR-Tactile group); or (3) reared by their mother (MR group). At PND 7, 14, or 21, electrophysiological properties and histological characteristics of the SU nerves were assessed. At PND 7, the electrophysiological properties and most histological parameters of the SU nerve did not differ among MR, AR, and AR-Tactile groups. By contrast, at PND 14 and/or 21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a significant reduction in myelin area and myelin thickness, which were accompanied by a reduction in axon area (day 21 only) compared to the nerves of MR rats. Tactile stimulation (AR-Tactile group) partially prevented most of these alterations. These results suggest that sensory cues from the mother and/or littermates during the first 7-14 PND are relevant for the proper development and function of the adult SU nerve. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 351-362, 2018. © 2017 Wiley Periodicals, Inc.

  11. Congenital salivary gland anlage tumor - in utero and postnatal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa; Calvo-Garcia, Maria A.; Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Division of Pediatric Surgery, Cincinnati, OH (United States); Elluru, Ravindhra G. [Cincinnati Children' s Hospital Medical Center, Division of Pediatric Otolaryngology, Cincinnati, OH (United States)

    2015-03-01

    We present a case of an infant with congenital salivary gland anlage tumor, with fetal and postnatal imaging. To the best of our knowledge, this is the first case describing the in utero imaging findings of salivary gland anlage tumor. A fetal MRI was performed secondary to the clinical finding of polyhydramnios, which identified a nasopharyngeal mass. Because findings were concerning for airway obstruction, the fetus was delivered by ex utero intrapartum treatment (EXIT) to airway procedure. A postnatal CT confirmed the findings of the fetal MRI. The lesion was resected when the baby was 4 days old and recovery was uneventful. (orig.)

  12. [Postnatal diagnosis of gastric volvulus revealing congenital diaphragmatic hernia].

    Science.gov (United States)

    Aprahamian, A; Nouyrigat, V; Grévent, D; Hervieux, E; Chéron, G

    2017-05-01

    Postnatally diagnosed congenital diaphragmatic hernias (CDH) are rare and have a better prognosis than those diagnosed prenatally. Postnatal symptoms can be respiratory, digestive, or mixed. Gastric volvulus can reveal CDH. Symptoms are pain, abdominal distension, and/or vomiting. Upper gastrointestinal barium X-ray radiography provides the diagnosis. Prognosis is related to early surgical management in complicated forms with intestinal occlusion or sub-occlusion. We report on an infant who presented with vomiting, which revealed gastric volvulus associated with a CDH. Progression was favorable after surgical treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Area 3a in the cat. I. A reevaluation of its location and architecture on the basis of Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining.

    Science.gov (United States)

    Avendaño, C; Verdu, A

    1992-07-15

    Current knowledge on the anatomy of area 3a of the cat mainly derives from the cyto- and myeloarchitectonic study of Hassler and Muhs-Clement (J Hirnforsch 6:377, 1964). Previous investigations in the cat had failed to identify a cortical region comparable to monkey's area 3a. In the present study, Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining techniques were applied to coronal and sagittal serial sections of the cat brain. Area 3a appears as a slender band of cortex between areas 4 and 3b, and in Nissl-stained sections it is mainly characterized by an attenuated granular layer IV, overlying a thin layer V with pyramidal cells of various sizes, including a few large ones. These cytoarchitectonic features are sufficient to differentiate area 3a from neighboring areas, although the borders between them are not sharp in many cases. After the Nissl staining, the acetylcholinesterase staining proved to be the most helpful in defining the structure and borders of area 3a. Acetylcholinesterase staining was dense in layer I (in contrast with a lighter staining of outer layer I in area 4), and light in layers II and IIIa, changing to moderate in IIIc and IV (a pattern which is accentuated in area 3b). Myelin and cytochrome oxidase techniques also yielded differential staining patterns of area 3a and neighboring areas 4 and 3b, although the borders were not easily drawn with these techniques. Whereas our cyto- and myeloarchitectonic findings were comparable to those of Hassler and Muhs-Clement ('64) and applied well to area 3a in the convexity of the hemisphere, we found that most of the area 3a described by these authors in the medial face of the hemisphere had a number of distinguishing architectonic (as well as connectional and physiological) features which enabled us to define it as a separate area (7m). The techniques we used to delineate area 3a are compatible with most current procedures of histo- and immunohistochemical staining of the brain

  14. Specific interaction of central nervous system myelin basic protein with lipids effects of basic protein on glucose leakage from liposomes

    NARCIS (Netherlands)

    Gould, R.M.; London, Y.

    1972-01-01

    The leakage from liposomes preloaded with glucose was continuously monitored in a Perkin-Elmer Model 356 dual beam spectrophotometer using an enzyme-linked assay system. The central nervous system myelin basic protein (A1 protein) caused a 3–4-fold increase in the rate of leakage from liposomes

  15. Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

    DEFF Research Database (Denmark)

    Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine

    2006-01-01

    was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP...

  16. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

    Science.gov (United States)

    Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

    2016-11-01

    The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (Pgross myelin structure and integrity appear unaffected (P>0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

  17. Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

    Science.gov (United States)

    Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

    2010-01-01

    The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

  18. Radioimmunoassay of the myelin basic protein in biological fluids, conditions improving sensitivity and specificity

    International Nuclear Information System (INIS)

    Delassalle, A.; Jacque, C.; Raoul, M.; Legrand, J.C.; Cesselin, F.; Drouet, J.

    1980-01-01

    The radioimmunoassay (RIA) for myelin basic protein (MBP) in biological fluids was reassessed in order to improve its sensitivity and eliminate some interferences. By using the pre-incubation technique and the charcoal-dextram-horse serum mixture for the separation step, the detection limit could be lowered to 200 pg/ml for cerebrospinal fluids (CSF), amniotic fluids (AF) and nervous tissue extracts and 600 pg/ml for sera. The RIA could be used directly on CSF, AF and nervous tissue extracts. Sera, however, had to be heated in citrate buffer at 100 0 C in order to discard interfering material. The present method is 10 to 20 times more sensitive than others previously published. Moreover, it can be applied to amniotic fluid. The biological fluids had to be promptly frozen to avoid degradation of MBP

  19. Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles

    International Nuclear Information System (INIS)

    Mendz, G.L.; Brown, L.R.; Martenson, R.E.

    1990-01-01

    The interactions of myelin basic protein and peptides derived from it with detergent micelles of lysophosphatidylglycerol, lysophosphatidylserine, palmitoyllysophosphatidic acid, and sodium lauryl sulfate, and with mixed micelles of the neutral detergent dodecylphosphocholine and the negatively charged detergent palmitoyllysophosphatidic acid, were investigated by 1 H NMR spectroscopy and circular dichroic spectropolarimetry. The results with single detergents suggested that there are discrete interaction sites in the protein molecule for neutral and anionic detergent micelles and that at least some of these sites are different for each type of detergent. The data on the binding of the protein and peptides to mixed detergent micelles suggested that intramolecular interactions in the intact protein and in one of the longer peptides limited the formation of helices and also that a balance between hydrophobic and ionic forces is achieved in the interactions of the peptides with the detergents. At high detergent/protein molar ratios, hydrophobic interactions appeared to be favored

  20. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B

    2010-01-01

    Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous...... NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O...... Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked....

  1. Protein-membrane interaction: effect of myelin basic protein on the dynamics of oriented lipids

    Energy Technology Data Exchange (ETDEWEB)

    Natali, F.; Relini, A.; Gliozzi, A.; Rolandi, R.; Cavatorta, P.; Deriu, A.; Fasano, A.; Riccio, P

    2003-08-01

    We have studied the effect of physiological amounts of myelin basic protein (MBP) on pure dimyristoyl L-{alpha}-phosphatidic acid (DMPA) oriented membranes. The investigation has been carried out using several complementary experimental methods to provide a detailed characterization of the proteo-lipid complexes. In particular, taking advantage of the power of the quasi-elastic neutron scattering (QENS) technique as optimal probe in biology, a significant effect is suggested to be induced by MBP on the anisotropy of lipid dynamics across the liquid-gel phase transition. Thus, the enhancement of the spatially restricted, vertical translation motion of DMPA is suggested to be the main responsible for the increased contribution of the out of plane lipid dynamics observed at 340 K.

  2. Analysis of relationship between demyelinating lesions and myelin basic protein in pancreatic encephalopathy

    Directory of Open Access Journals (Sweden)

    HUANG Boru

    2015-05-01

    Full Text Available Pancreatic encephalopathy (PE is one of the severe complications of severe acute pancreatitis (SAP. Early diagnosis mostly depends on the history of disease as well as clinical symptoms and signs. PE progresses rapidly and is often complicated by multiple organ dysfunction, and it may finally develop into multiple organ failure with a high fatality rate if not treated in time. It is currently known that demyelination is one of the important pathological features of this disease, with fat-soluble demyelination of cerebral gray matter and white matter, as well as inflammatory changes such as hemorrhage and edema. The target antigen of demyelinating lesions, however, is myelin basic protein (MBP. This paper reviews the changes in MBP levels in the demyelinating lesions of the central nervous system among PE patients, with the purpose of providing clues for the early diagnosis and prognostic study of demyelinating lesions in PE.

  3. Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus

    DEFF Research Database (Denmark)

    Jensen, M B; Poulsen, F R; Finsen, B

    2000-01-01

    to 35 days after transection of the entorhino-hippocampal perforant path axonal projection. In situ hybridization analysis showed that anterograde axonal and terminal degeneration lead to upregulated oligodendrocyte MBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratum...... axonal and terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. Oligodendrocyte MBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratum radiatum, stratum pyramidale and stratum oriens...... of CA1, areas that were unaffected by perforant path transection. These results provide strong evidence that oligodendrocyte MBP gene expression can be regulated by axonal sprouting independently of microglial activation in the injured adult CNS....

  4. Divergent Immunomodulation Capacity of Individual Myelin Peptides—Components of Liposomal Therapeutic against Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Vilena V. Ivanova

    2017-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by demyelination and consequent neuron injury. Although the pathogenesis of MS is largely unknown, a breach in immune self-tolerance to myelin followed by development of autoreactive encephalitogenic T cells is suggested to play the central role. The myelin basic protein (MBP is believed to be one of the main targets for autoreactive lymphocytes. Recently, immunodominant MBP peptides encapsulated into the mannosylated liposomes, referred as Xemys, were shown to suppress development of experimental autoimmune encephalomyelitis, a rodent model of MS, and furthermore passed the initial stage of clinical trials. Here, we investigated the role of individual polypeptide components [MBP peptides 46–62 (GH17, 124–139 (GK16, and 147–170 (QR24] of this liposomal peptide therapeutic in cytokine release and activation of immune cells from MS patients and healthy donors. The overall effects were assessed using peripheral blood mononuclear cells (PBMCs, whereas alterations in antigen-presenting capacities were studied utilizing plasmacytoid dendritic cells (pDCs. Among three MBP-immunodominant peptides, QR24 and GK16 activated leukocytes, while GH17 was characterized by an immunosuppressive effect. Peptides QR24 and GK16 upregulated CD4 over CD8 T cells and induced proliferation of CD25+ cells, whereas GH17 decreased the CD4/CD8 T cell ratio and had limited effects on CD25+ T cells. Accordingly, components of liposomal peptide therapeutic differed in upregulation of cytokines upon addition to PBMCs and pDCs. Peptide QR24 was evidently more effective in upregulation of pro-inflammatory cytokines, whereas GH17 significantly increased production of IL-10 through treated cells. Altogether, these data suggest a complexity of action of the liposomal peptide therapeutic that does not seem to involve simple helper T cells (Th-shift but rather the rebalancing of the immune system.

  5. Impact of morphometry, myelinization and synaptic current strength on spike conduction in human and cat spiral ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Frank Rattay

    Full Text Available Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction.Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA synaptic stimuli.Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea.

  6. Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation

    Directory of Open Access Journals (Sweden)

    Nadia eGarcía-Mateo

    2014-11-01

    Full Text Available Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood.Apolipoprotein D (ApoD is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA, also interacts with lysophosphatidylcholine (LPC in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii ApoD controls the basal and injury-triggered levels of LPC and AA; (iv ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation.Regulation of macrophage behaviour by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration

  7. Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

    Science.gov (United States)

    Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

    2013-01-01

    Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat

  8. What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

    Directory of Open Access Journals (Sweden)

    Taylor Chomiak

    2009-11-01

    Full Text Available The biological process underlying axonal myelination is complex and often prone to injury and disease. The ratio of the inner axonal diameter to the total outer diameter or g-ratio is widely utilized as a functional and structural index of optimal axonal myelination. Based on the speed of fiber conduction, Rushton was the first to derive a theoretical estimate of the optimal g-ratio of 0.6 [1]. This theoretical limit nicely explains the experimental data for myelinated axons obtained for some peripheral fibers but appears significantly lower than that found for CNS fibers. This is, however, hardly surprising given that in the CNS, axonal myelination must achieve multiple goals including reducing conduction delays, promoting conduction fidelity, lowering energy costs, and saving space.In this study we explore the notion that a balanced set-point can be achieved at a functional level as the micro-structure of individual axons becomes optimized, particularly for the central system where axons tend to be smaller and their myelin sheath thinner. We used an intuitive yet novel theoretical approach based on the fundamental biophysical properties describing axonal structure and function to show that an optimal g-ratio can be defined for the central nervous system (approximately 0.77. Furthermore, by reducing the influence of volume constraints on structural design by about 40%, this approach can also predict the g-ratio observed in some peripheral fibers (approximately 0.6.These results support the notion of optimization theory in nervous system design and construction and may also help explain why the central and peripheral systems have evolved different g-ratios as a result of volume constraints.

  9. What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

    Science.gov (United States)

    Chomiak, Taylor; Hu, Bin

    2009-11-13

    The biological process underlying axonal myelination is complex and often prone to injury and disease. The ratio of the inner axonal diameter to the total outer diameter or g-ratio is widely utilized as a functional and structural index of optimal axonal myelination. Based on the speed of fiber conduction, Rushton was the first to derive a theoretical estimate of the optimal g-ratio of 0.6 [1]. This theoretical limit nicely explains the experimental data for myelinated axons obtained for some peripheral fibers but appears significantly lower than that found for CNS fibers. This is, however, hardly surprising given that in the CNS, axonal myelination must achieve multiple goals including reducing conduction delays, promoting conduction fidelity, lowering energy costs, and saving space. In this study we explore the notion that a balanced set-point can be achieved at a functional level as the micro-structure of individual axons becomes optimized, particularly for the central system where axons tend to be smaller and their myelin sheath thinner. We used an intuitive yet novel theoretical approach based on the fundamental biophysical properties describing axonal structure and function to show that an optimal g-ratio can be defined for the central nervous system (approximately 0.77). Furthermore, by reducing the influence of volume constraints on structural design by about 40%, this approach can also predict the g-ratio observed in some peripheral fibers (approximately 0.6). These results support the notion of optimization theory in nervous system design and construction and may also help explain why the central and peripheral systems have evolved different g-ratios as a result of volume constraints.

  10. Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

    Directory of Open Access Journals (Sweden)

    Yakov Lomakin

    2017-07-01

    Full Text Available Multiple sclerosis (MS is an autoimmune chronic inflammatory disease of the central nervous system (CNS. Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV latent membrane protein 1 (LMP1. In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

  11. Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

    Science.gov (United States)

    Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading. PMID:28729867

  12. Exposure to the Epstein-Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo.

    Science.gov (United States)

    Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo . We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20-50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

  13. A survey of pregnant and postnatal women, clinic attendees and ...

    African Journals Online (AJOL)

    A survey of pregnant and postnatal women, clinic attendees and maternity staff regarding the presence of birth companions during labour and delivery. ... Conclusion: The involvement of birth companions supporting women during childbirth could be promoted as a low cost preventive intervention to improve maternal and ...

  14. Equine locomotory muscles : postnatal development and the influence of exercise

    NARCIS (Netherlands)

    Dingboom, Elizabeth Gerardina

    2002-01-01

    The Dutch warmblood horse is widely used in different types of sport. The individual capacity to perform depends on factors as character and the quality of the cardiopulmonary and musculoskeletal system. These factors are partly genetically determined; in the postnatal phase of growth and maturation

  15. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    2016-11-01

    Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD.

  16. Early postnatal calcium and phosphorus metabolism in preterm infants

    NARCIS (Netherlands)

    Christmann, Viola; de Grauw, Anne M.; Visser, Reina; Matthijsse, René P.; van Goudoever, Johannes B.; van Heijst, Arno F. J.

    2014-01-01

    Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake. Preterm infants,

  17. Early postnatal calcium and phosphorus metabolism in preterm infants

    NARCIS (Netherlands)

    Christmann, V.; Grauw, A.M. de; Visser, R.; Matthijsse, R.P.; Goudoever, J.B. van; Heijst, A.F.J. van

    2014-01-01

    OBJECTIVES: Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake.

  18. Postnatal depression - an examination of psychosocial factors | Mills ...

    African Journals Online (AJOL)

    Postnatal depression (PND) has been underreported in South Africa. This retrospective study investigated factors which appear to predispose women to PND. Two groups, one consisting of women who suffered from PND and the other of women free of this complaint, provided information on a number of biological, ...

  19. Postnatal morphology of hematoencephalic barrier in hypoxic lesion

    Directory of Open Access Journals (Sweden)

    E. V. Kikhtenko

    2012-12-01

    Full Text Available In infants with perinatal hypoxic lesion of the central nervous system swelling and death of the endothelium, thickening of the capillary basement membranes, karyorrhexis and plasmorrhexis of astrocytes are observed. The severity and degree of pathological changes depends on the time of hypoxic exposure (antenatal or intrapartum period and the term of postnatal life.

  20. Postnatal cranial ultrasonographic findings in feto-fetal transfusion syndrome.

    NARCIS (Netherlands)

    Breysem, L.; Naulaers, G.; Deprest, J.; Schoubroeck, D.V.; Daniels, H.; Lammens, M.M.Y.; Smet, M.H.

    2002-01-01

    Our objective was a retrospective evaluation of cranial US in survivors of twin pregnancy with feto-fetal transfusion syndrome (FFTS), with knowledge of prenatal treatment and neonatal/postnatal clinical data. In 18 pregnancies with FFTS (January 1996 to May 2000), pregnancy management and outcome,

  1. Postnatal Growth Rates of Hummingbirds : Review and New Records

    NARCIS (Netherlands)

    Freymann, Bernd P.; Schuchmann, Karl-Ludwig

    2008-01-01

    We review the published information on postnatal growth rates of hummingbirds (13 species), and report previously unpublished records for nine additional trochilid species. The allometric relationship based on the log(10)-transformed data of K (logistic growth rate constant) and body mass has a

  2. Decoding cell signalling and regulation of oligodendrocyte differentiation.

    Science.gov (United States)

    Santos, A K; Vieira, M S; Vasconcellos, R; Goulart, V A M; Kihara, A H; Resende, R R

    2018-05-22

    Oligodendrocytes are fundamental for the functioning of the nervous system; they participate in several cellular processes, including axonal myelination and metabolic maintenance for astrocytes and neurons. In the mammalian nervous system, they are produced through waves of proliferation and differentiation, which occur during embryogenesis. However, oligodendrocytes and their precursors continue to be generated during adulthood from specific niches of stem cells that were not recruited during development. Deficiencies in the formation and maturation of these cells can generate pathologies mainly related to myelination. Understanding the mechanisms involved in oligodendrocyte development, from the precursor to mature cell level, will allow inferring therapies and treatments for associated pathologies and disorders. Such mechanisms include cell signalling pathways that involve many growth factors, small metabolic molecules, non-coding RNAs, and transcription factors, as well as specific elements of the extracellular matrix, which act in a coordinated temporal and spatial manner according to a given stimulus. Deciphering those aspects will allow researchers to replicate them in vitro in a controlled environment and thus mimic oligodendrocyte maturation to understand the role of oligodendrocytes in myelination in pathologies and normal conditions. In this study, we review these aspects, based on the most recent in vivo and in vitro data on oligodendrocyte generation and differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Cerebral pathology and neuropsychological effects. Differential effects of cranial radiation as a function of age

    International Nuclear Information System (INIS)

    Dowell, R.E. Jr.; Copeland, D.R.

    1987-01-01

    Cranial radiation therapy (CRT) has been associated with an increased incidence of neuropsychological impairments and pathologic changes in the CNS among children. However, findings regarding a causal relationship between CRT and neurobehavioral impairments and the differential impact of CRT as a function of treatment age have been equivocal. Inconsistent findings may be attributed to the current research focus on description of impairments to the neglect of a larger theoretical framework and the failure of investigators to integrate findings from the various disciplines involved in assessing CRT effects. Two theories regarding the etiology of CRT effects on neuropsychological functions have been proposed. The myelination hypothesis suggests that CRT effects are attributable to direct effects on myelin synthesis. Findings indicating that the child is in a state of particular vulnerability to teratogens due to the rapid growth phase of myelin during the first 48 months of life provide the basis for this hypothesis. The myelination hypothesis predicts a differential effect for CRT as a function of age/maturation. The vascular hypothesis proposes that CRT effects are due to pathological changes in vascular tissues. Results indicating prominent white matter changes among some CRT recipients provide the basis for this hypothesis. The vascular hypothesis predicts no age effect or an inverse age effect; it places more emphasis on the relationship between indices of cerebral blood flow and neuropsychological test performance. Two basic mechanisms underlying the effects of CRT are outlined to provide a theoretical framework on which future research may be based. 29 references

  4. Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

    Science.gov (United States)

    Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

    2013-01-01

    Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

  5. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder.

    Science.gov (United States)

    Hadjkacem, Imen; Ayadi, Héla; Turki, Mariem; Yaich, Sourour; Khemekhem, Khaoula; Walha, Adel; Cherif, Leila; Moalla, Yousr; Ghribi, Farhat

    To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD) by comparing them to their siblings without autistic disorders. The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014). It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p=0.03 and p=0.042). In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases), long duration of delivery and prematurity (18% of cases for each factor), while postnatal factors were represented principally by respiratory infections (24%). As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others), as determinant variables for the genesis of ASD. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  6. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    Full Text Available Abstract Objective: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD by comparing them to their siblings without autistic disorders. Method: The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014. It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Results: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p = 0.03 and p = 0.042. In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases, long duration of delivery and prematurity (18% of cases for each factor, while postnatal factors were represented principally by respiratory infections (24%. As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD.

  7. Predictors of intelligence at the age of 5: family, pregnancy and birth characteristics, postnatal influences, and postnatal growth.

    Science.gov (United States)

    Eriksen, Hanne-Lise Falgreen; Kesmodel, Ulrik Schiøler; Underbjerg, Mette; Kilburn, Tina Røndrup; Bertrand, Jacquelyn; Mortensen, Erik Lykke

    2013-01-01

    Parental education and maternal intelligence are well-known predictors of child IQ. However, the literature regarding other factors that may contribute to individual differences in IQ is inconclusive. The aim of this study was to examine the contribution of a number of variables whose predictive status remain unclarified, in a sample of basically healthy children with a low rate of pre- and postnatal complications. 1,782 5-year-old children sampled from the Danish National Birth Cohort (2003-2007) were assessed with a short form of the Wechsler Preschool and Primary Scale of Intelligence - Revised. Information on parental characteristics, pregnancy and birth factors, postnatal influences, and postnatal growth was collected during pregnancy and at follow-up. A model including study design variables and child's sex explained 7% of the variance in IQ, while parental education and maternal IQ increased the explained variance to 24%. Other predictors were parity, maternal BMI, birth weight, breastfeeding, and the child's head circumference and height at follow-up. These variables, however, only increased the explained variance to 29%. The results suggest that parental education and maternal IQ are major predictors of IQ and should be included routinely in studies of cognitive development. Obstetrical and postnatal factors also predict IQ, but their contribution may be of comparatively limited magnitude.

  8. Predictors of intelligence at the age of 5: family, pregnancy and birth characteristics, postnatal influences, and postnatal growth.

    Directory of Open Access Journals (Sweden)

    Hanne-Lise Falgreen Eriksen

    Full Text Available Parental education and maternal intelligence are well-known predictors of child IQ. However, the literature regarding other factors that may contribute to individual differences in IQ is inconclusive. The aim of this study was to examine the contribution of a number of variables whose predictive status remain unclarified, in a sample of basically healthy children with a low rate of pre- and postnatal complications. 1,782 5-year-old children sampled from the Danish National Birth Cohort (2003-2007 were assessed with a short form of the Wechsler Preschool and Primary Scale of Intelligence - Revised. Information on parental characteristics, pregnancy and birth factors, postnatal influences, and postnatal growth was collected during pregnancy and at follow-up. A model including study design variables and child's sex explained 7% of the variance in IQ, while parental education and maternal IQ increased the explained variance to 24%. Other predictors were parity, maternal BMI, birth weight, breastfeeding, and the child's head circumference and height at follow-up. These variables, however, only increased the explained variance to 29%. The results suggest that parental education and maternal IQ are major predictors of IQ and should be included routinely in studies of cognitive development. Obstetrical and postnatal factors also predict IQ, but their contribution may be of comparatively limited magnitude.

  9. Foxa2 and Pdx1 cooperatively regulate postnatal maturation of pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Aimée Bastidas-Ponce

    2017-06-01

    Full Text Available Objective: The transcription factors (TF Foxa2 and Pdx1 are key regulators of beta-cell (β-cell development and function. Mutations of these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes of the young (MODY, pancreas agenesis, or diabetes susceptibility in human. Although Foxa2 has been shown to directly regulate Pdx1 expression during mouse embryonic development, the impact of this gene regulatory interaction on postnatal β-cell maturation remains obscure. Methods: In order to easily monitor the expression domains of Foxa2 and Pdx1 and analyze their functional interconnection, we generated a novel double knock-in homozygous (FVFPBFDHom fluorescent reporter mouse model by crossing the previously described Foxa2-Venus fusion (FVF with the newly generated Pdx1-BFP (blue fluorescent protein fusion (PBF mice. Results: Although adult PBF homozygous animals exhibited a reduction in expression levels of Pdx1, they are normoglycemic. On the contrary, despite normal pancreas and endocrine development, the FVFPBFDHom reporter male animals developed hyperglycemia at weaning age and displayed a reduction in Pdx1 levels in islets, which coincided with alterations in β-cell number and islet architecture. The failure to establish mature β-cells resulted in loss of β-cell identity and trans-differentiation towards other endocrine cell fates. Further analysis suggested that Foxa2 and Pdx1 genetically and functionally cooperate to regulate maturation of adult β-cells. Conclusions: Our data show that the maturation of pancreatic β-cells requires the cooperative function of Foxa2 and Pdx1. Understanding the postnatal gene regulatory network of β-cell maturation will help to decipher pathomechanisms of diabetes and identify triggers to regenerate dedifferentiated β-cell mass. Keywords: Foxa2, Pdx1, β-Cell maturation, β-Cell identity, Trans-differentiation

  10. Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation.

    Science.gov (United States)

    Deng, Tao; Postnikov, Yuri; Zhang, Shaofei; Garrett, Lillian; Becker, Lore; Rácz, Ildikó; Hölter, Sabine M; Wurst, Wolfgang; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabe; Bustin, Michael

    2017-04-07

    An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the presence of HMGN proteins is required for proper expression of neural differentiation genes during embryonic stem cell differentiation. Specifically, we demonstrate that the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior. Published by Oxford University Press on behalf of Nucleic Acids Research 2016.

  11. Modelling the presence of myelin and oedema in the brain based on multi-parametric quantitative MRI

    Directory of Open Access Journals (Sweden)

    Marcel eWarntjes

    2016-02-01

    Full Text Available The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and oedema in the brain. The model relates simultaneous measurement of R1 and R2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume and excess parenchymal water partial volume. The model parameters were obtained using spatially normalised brain images of a group of 20 healthy controls. The pathological brain was modelled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of oedema. The method was tested on spatially normalised brain images of a group of 20 age-matched multiple sclerosis (MS patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL, a 38 mL smaller myelin volume (119 vs. 157 mL and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL. Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6±1.5% lower for grey matter (GM structures and 2.8±1.0% lower for white matter (WM structures. The excess parenchymal water partial volume was 9±10% larger for GM and 5±2% larger for WM. Manually placed ROIs indicated that the results using the template ROIs may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects, a 45-year-old healthy subject, a 72-year-old healthy subject and a 45-year-old MS patient. The observed results agreed with the expected behaviour considering both age and disease. In conclusion, the proposed model may provide clinically important parameters such as the total brain volume, degree of myelination and degree of oedema, based on

  12. Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

    Science.gov (United States)

    Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

    2016-11-01

    Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

  13. Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability.

    Science.gov (United States)

    Kropp, Peter A; Dunn, Jennifer C; Carboneau, Bethany A; Stoffers, Doris A; Gannon, Maureen

    2018-04-01

    The transcription factors pancreatic and duodenal homeobox 1 (Pdx1) and onecut1 (Oc1) are coexpressed in multipotent pancreatic progenitors (MPCs), but their expression patterns diverge in hormone-expressing cells, with Oc1 expression being extinguished in the endocrine lineage and Pdx1 being maintained at high levels in β-cells. We previously demonstrated that cooperative function of these two factors in MPCs is necessary for proper specification and differentiation of pancreatic endocrine cells. In those studies, we observed a persistent decrease in expression of the β-cell maturity factor MafA. We therefore hypothesized that Pdx1 and Oc1 cooperativity in MPCs impacts postnatal β-cell maturation and function. Here our model of Pdx1-Oc1 double heterozygosity was used to investigate the impact of haploinsufficiency for both of these factors on postnatal β-cell maturation, function, and adaptability. Examining mice at postnatal day (P) 14, we observed alterations in pancreatic insulin content in both Pdx1 heterozygotes and double heterozygotes. Gene expression analysis at this age revealed significantly decreased expression of many genes important for glucose-stimulated insulin secretion (e.g., Glut2, Pcsk1/2, Abcc8) exclusively in double heterozygotes. Analysis of P14 islets revealed an increase in the number of mixed islets in double heterozygotes. We predicted that double-heterozygous β-cells would have an impaired ability to respond to stress. Indeed, we observed that β-cell proliferation fails to increase in double heterozygotes in response to either high-fat diet or placental lactogen. We thus report here the importance of cooperation between regulatory factors early in development for postnatal islet maturation and adaptability.

  14. Developmental and behavioral effects of postnatal amitraz exposure in rats

    Directory of Open Access Journals (Sweden)

    J. Palermo-Neto

    1997-08-01

    Full Text Available The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg on the same days. A total of 18 different litters (9 of them control and 9 experimental born after a 21-day gestation were used. The results showed that the median effective time (ET50 for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively. The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds to perform the surface righting reflex on postnatal days (PND 3 (25.0 ± 2.0, 4 (12.3 ± 1.2 and 5 (8.7 ± 0.9 in relation to controls (10.6 ± 1.2; 4.5 ± 0.6 and 3.4 ± 0.4, respectively; the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 ± 11 and 17 (124 ± 12, and 16 (104 ± 9, 17 (137 ± 9 and 18 (106 ± 8, respectively. Data on spontaneous motor activity of the control male and female pups were 59 ± 11 and 69 ± 10 for days 16 and 17 and 49 ± 9, 48 ± 7 and 56 ± 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate

  15. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana; Krarup, Christian

    2013-01-01

    Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate...... whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using...... threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated...

  16. Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS

    DEFF Research Database (Denmark)

    Thurnherr, Tina; Benninger, Yves; Wu, Xunwei

    2006-01-01

    . This was characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal accumulation of cytoplasm in the inner tongue...... of the oligodendrocyte process, and we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage-dependent way to regulate myelination....

  17. Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

    Science.gov (United States)

    Veber, Daniela; Scalabrino, Giuseppe

    2015-12-15

    We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

    2014-04-15

    Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

  19. Prenatal and postnatal evaluation of polymicrogyria with band heterotopia.

    Science.gov (United States)

    Nagaraj, Usha D; Hopkin, Robert; Schapiro, Mark; Kline-Fath, Beth

    2017-09-01

    The coexistence of band heterotopia and polymicrogyria is extremely rare though it has been reported in the presence of corpus callosum anomalies and megalencephaly. We present prenatal and postnatal MRI findings of a rare case of diffuse cortical malformation characterized by polymicrogyria and band heterotopia. Agenesis of the corpus callosum and megalencephaly were also noted. In addition, bilateral closed-lip schizencephaly was identified on postnatal MRI, which has not been previously reported with this combination of imaging findings. Polymicrogyria with band heterotopia can occur and can be diagnosed with fetal MRI. The coexistence of corpus callosum anomalies and megalencephaly comprises a rare phenotype that has been previously described, suggesting an underlying genetic abnormality.

  20. Prenatal and postnatal evaluation of polymicrogyria with band heterotopia

    Directory of Open Access Journals (Sweden)

    Usha D. Nagaraj, MD

    2017-09-01

    Full Text Available The coexistence of band heterotopia and polymicrogyria is extremely rare though it has been reported in the presence of corpus callosum anomalies and megalencephaly. We present prenatal and postnatal MRI findings of a rare case of diffuse cortical malformation characterized by polymicrogyria and band heterotopia. Agenesis of the corpus callosum and megalencephaly were also noted. In addition, bilateral closed-lip schizencephaly was identified on postnatal MRI, which has not been previously reported with this combination of imaging findings. Polymicrogyria with band heterotopia can occur and can be diagnosed with fetal MRI. The coexistence of corpus callosum anomalies and megalencephaly comprises a rare phenotype that has been previously described, suggesting an underlying genetic abnormality.

  1. Sex-based differences in gene expression in hippocampus following postnatal lead exposure

    International Nuclear Information System (INIS)

    Schneider, J.S.; Anderson, D.W.; Sonnenahalli, H.; Vadigepalli, R.

    2011-01-01

    The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 ± 2.1 μg/dl and 27.1 ± 1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: → Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. → At least one set of genes was affected in opposite directions in males and females. → Differentially expressed genes were associated with diverse biological pathways.

  2. Early postnatal docosahexaenoic acid levels and improved preterm brain development

    OpenAIRE

    Tam, Emily W.Y.; Chau, Vann; Barkovich, A. James; Ferriero, Donna M.; Miller, Steven P.; Rogers, Elizabeth E.; Grunau, Ruth E.; Synnes, Anne R.; Xu, Duan; Foong, Justin; Brant, Rollin; Innis, Sheila M.

    2016-01-01

    Background Preterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes. Methods A cohort of 60 preterm newborns (24?32 weeks GA) was assessed using early and near-term MRI studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 months corrected age was assessed...

  3. Quality of life, postnatal depression and baby gender.

    Science.gov (United States)

    de Tychey, Claude; Briançon, Serge; Lighezzolo, Joëlle; Spitz, Elisabeth; Kabuth, Bernard; de Luigi, Valerie; Messembourg, Catherine; Girvan, Françoise; Rosati, Aurore; Thockler, Audrey; Vincent, Stephanie

    2008-02-01

    To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.

  4. Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function.

    Science.gov (United States)

    Makinodan, Manabu; Ikawa, Daisuke; Yamamuro, Kazuhiko; Yamashita, Yasunori; Toritsuka, Michihiro; Kimoto, Sohei; Yamauchi, Takahira; Okumura, Kazuki; Komori, Takashi; Fukami, Shin-Ichi; Yoshino, Hiroki; Kanba, Shigenobu; Wanaka, Akio; Kishimoto, Toshifumi

    2017-07-14

    Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice. While mice who underwent re-socialization with socially isolated mice after juvenile social isolation (Re-IS mice) demonstrated less mPFC activity during exposure to a strange mouse, as well as thinner myelin in the mPFC than controls, mice who underwent re-socialization with socially housed mice after juvenile social isolation (Re-SH mice) caught up with the controls in terms of most mPFC functions, as well as myelination. Moreover, social interaction of Re-IS mice was reduced as compared to controls, but Re-SH mice showed an amount of social interaction comparable to that of controls. These results suggest that the mode of re-socialization after juvenile social isolation has significant effects on myelination in the mPFC and the attendant functions in mice, indicating the importance of appropriate psychosocial intervention after social isolation.

  5. Prenatal and Postnatal Cell Phone Exposures and Headaches in Children.

    Science.gov (United States)

    Sudan, Madhuri; Kheifets, Leeka; Arah, Onyebuchi; Olsen, Jorn; Zeltzer, Lonnie

    2012-12-05

    Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their children reached age seven years, mothers completed a questionnaire regarding the child's health, behaviors, and exposures. We used multivariable adjusted models to relate prenatal only, postnatal only, or both prenatal and postnatal cell phone exposure to whether the child had migraines and headache-related symptoms. Our analyses included data from 52,680 children. Children with cell phone exposure had higher odds of migraines and headache-related symptoms than children with no exposure. The odds ratio for migraines was 1.30 (95% confidence interval: 1.01-1.68) and for headache-related symptoms was 1.32 (95% confidence interval: 1.23-1.40) for children with both prenatal and postnatal exposure. In this study, cell phone exposures were associated with headaches in children, but the associations may not be causal given the potential for uncontrolled confounding and misclassification in observational studies such as this. However, given the widespread use of cell phones, if a causal effect exists it would have great public health impact.

  6. Postnatal development of the myenteric plexus in cat stomach.

    Science.gov (United States)

    Lolova, I; Itsev, D

    1983-01-01

    The postnatal development of the myenteric plexus in cat stomach has been studied at birth, on the 14th, 30th, 45th and 180th postnatal days, using light- and electronmicroscopic methods. In newborn kittens the main network of the Auerbach plexus is well formed, but the myenteric ganglia are composed of nerve cells with different maturity and a scarce neuropile. During the first two postnatal weeks the dimensions of the ganglia increase owing to the increase of the nerve bodies and the rising number of glials cells and intercellular fibres. This is accompanied by a potentiation of the AChE-activity, mainly in the nerve cell bodies and to a lesser extent in the neuropile. Impregnation reveals different in calibre and form nerve fibres and terminals. Different ultrastructural types of neurones are identified on the 14th day. Later development is expressed in the formation of large compact ganglia and thick connecting strands. The number of AChE-positive fibres in the neuropile increases. Owing to the increase in the cell organelles and their more advanced maturity, it is possible to define the ultrastructural type of an ever increasing number of neurones.

  7. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis.

    Science.gov (United States)

    Angelova, Alexandra; Tiveron, Marie-Catherine; Cremer, Harold; Beclin, Christophe

    2018-01-01

    In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

  8. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandra Angelova

    2018-02-01

    Full Text Available In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

  9. Postnatal TLR2 activation impairs learning and memory in adulthood.

    Science.gov (United States)

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve.

    Science.gov (United States)

    Robert, A; Jirounek, P

    1998-07-01

    Changes in membrane potential and potassium concentration in the extracellular space ([K+]e) of rabbit vagus nerve were measured simultaneously during electrical activity and during the period of recovery using a modified sucrose-gap method and potassium-sensitive microelectrodes. After stimulation for 15 s at 15 Hz the main activity-induced increase in [K+]e reached 16.9 mM. This increase in [K+]e was paralleled by a depolarization of the preparation. The period of activity was followed by a post-tetanic hyperpolarization (PTH) lasting tens of seconds, generated by the axonal electrogenic Na+-K+ pump and to a lesser extent by the pump of the surrounding Schwann cells. The amplitude of the PTH dramatically increased in experiments in which inward currents were blocked by removal of Cl– or after application of Cs+ or Ba2+, indicating that under normal conditions the current generated by the Na+-K+ pump is strongly short-circuited. A pharmacological and kinetic study showed that these currents are: (1) the hyperpolarization-activated current I h, and (2) the inwardly rectifying I KIR current. The results show that the latter originates from Schwann cells. Our data indicate that in non-myelinated nerves there is a subtle association of inward ionic channels which (1) helps the cell to maintain an optimal membrane potential after a period of activity, and (2) contributes to the removal of excess K+ from the extracellular space.

  11. Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat

    Directory of Open Access Journals (Sweden)

    Guadalupe Soto-Rodriguez

    2015-01-01

    Full Text Available Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT2 Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4, which might account for the demyelination in the taiep rat.

  12. Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.

    Science.gov (United States)

    Kim, Joo-Won; Naidich, Thomas P; Joseph, Joshmi; Nair, Divya; Glasser, Matthew F; O'halloran, Rafael; Doucet, Gaelle E; Lee, Won Hee; Krinsky, Hannah; Paulino, Alejandro; Glahn, David C; Anticevic, Alan; Frangou, Sophia; Xu, Junqian

    2018-03-26

    In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi-automated habenula segmentation methods have been reported, the test-retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra- and inter-site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously proposed semi-automated myelin contrast-based method and its fully-automated version, as well as a previously published manual geometry-based method. The habenula segmentation using our semi-automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi-automated habenula segmentation showed reliable and reproducible habenula localization, while its fully-automated version offers an efficient way for large sample analysis. © 2018 Wiley Periodicals, Inc.

  13. Multiple epitopes in a dodecapeptide of myelin basic protein determined bymonoclonal antibodies

    International Nuclear Information System (INIS)

    Price, J.O.; Whitaker, J.N.; Vasu, R.I.; Metzger, D.W.

    1986-01-01

    Three custom synthesized myelin basic protein (MBP) peptides, bovine peptide 79-88, human peptide 80-89, and human peptide 82-91, were used to produce four murine monoclonal antibodies (MAb) that were selected on the basis of reaction in a solid phase radioimmunoassay (SRIA) with human MBP. The MAb were compared with respect to antigen specificity against intact MBP and 10 overlapping MBP peptides. One MAb recognized an epitope near the amino-terminus of bovine MBP peptide 79-88. A second MAb was directed towards an epitope that is more reactive in human MBP peptide 45-89 than in intact MBP, but is not recognized in any of the small MBP peptides examined. The third MAb detected an epitope near the middle of human MBP peptide 80-89, whereas the fourth MAb reacted with the carboxyl-terminal portion of human MBP peptide 82-91. Epitopes recognized in SRIA were sometimes not detected by the same MAb in a fluid phase double antibody radioimmunoassay. These results demonstrate the multiplicity of potential epitopes in a dodecapeptide of MBP and do not support the concept of a single, dominant epitope in the region of MBP peptide 80-89

  14. Characterization of fatty acid binding by the P2 myelin protein

    International Nuclear Information System (INIS)

    Gudaitis, P.G.; Weise, M.J.

    1987-01-01

    In recent years, significant sequence homology has been found between the P2 protein of peripheral myelin and intracellular retinoid- and fatty acid-binding proteins. They have found that salt extracts of bovine intradural nerve roots contain the P2 basic protein in association with free fatty acid. Preliminary results from quantitative analyses showed a ratio of 0.4-1.1 fatty acid (mainly oleate and palmitate) per P2 molecule. P2/ligand interactions were partially characterized using ( 3 H)-oleate in gel permeation assays and binding studies using lipidex to separated bound and free fatty acid. Methyloleate was found to displace ( 3 H)-oleate from P2, indicating that ligand binding interactions are predominantly hydrophobic in nature. On the other hand, myristic acid and retinol did not inhibit the binding of oleate to the protein, results consistent with a decided affinity for long chain fatty acids but not for the retinoids. The binding between P2 and oleic acid showed an apparent Kd in the micromolar range, a value comparable to those found for other fatty acid-binding proteins. From these results they conclude that P2 shares not only structural homology with certain fatty acid binding proteins but also an ability to bind long chain fatty acids. Although the significance of these similarities is not yet clear, they may, by analogy, expect P2 to have a role in PNS lipid metabolism

  15. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction.

    Science.gov (United States)

    Mattei, César; Marquais, Michel; Schlumberger, Sébastien; Molgó, Jordi; Vernoux, Jean-Paul; Lewis, Richard J; Benoit, Evelyne

    2010-10-01

    Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers. Copyright 2009 Elsevier Ltd. All rights reserved.

  16. A New Method for Automated Identification and Morphometry of Myelinated Fibers Through Light Microscopy Image Analysis.

    Science.gov (United States)

    Novas, Romulo Bourget; Fazan, Valeria Paula Sassoli; Felipe, Joaquim Cezar

    2016-02-01

    Nerve morphometry is known to produce relevant information for the evaluation of several phenomena, such as nerve repair, regeneration, implant, transplant, aging, and different human neuropathies. Manual morphometry is laborious, tedious, time consuming, and subject to many sources of error. Therefore, in this paper, we propose a new method for the automated morphometry of myelinated fibers in cross-section light microscopy images. Images from the recurrent laryngeal nerve of adult rats and the vestibulocochlear nerve of adult guinea pigs were used herein. The proposed pipeline for fiber segmentation is based on the techniques of competitive clustering and concavity analysis. The evaluation of the proposed method for segmentation of images was done by comparing the automatic segmentation with the manual segmentation. To further evaluate the proposed method considering morphometric features extracted from the segmented images, the distributions of these features were tested for statistical significant difference. The method achieved a high overall sensitivity and very low false-positive rates per image. We detect no statistical difference between the distribution of the features extracted from the manual and the pipeline segmentations. The method presented a good overall performance, showing widespread potential in experimental and clinical settings allowing large-scale image analysis and, thus, leading to more reliable results.

  17. Myelin basic protein determination in cerebro-spinal fluid of children with tuberculous meningitis

    International Nuclear Information System (INIS)

    Samuel, A.M.; Dhalla, A.S.; Mazarello, T.

    1986-01-01

    Myelin basic protein (MBP), an indicator of neural tissue damage in cerebro-spinal fluid, was studied in patients with tuberculous meningitis (TBM). MBP levels were elevated in 62% of the cases of TBM, the levels being 13.3+-18.8 ng/mL, compared with control levels of 1.34+-0.55 ng/mL(p<0.001). MBP level was related to certain clinical features of the disease, such as level of consciousness, neurological characteristics associated with signs of raised intracranial tension and the presence of arteritis associated with hydrocephalus. However, its greatest significance was its correlation with the progress of disease. Persistence of high levels of MBP over a period of a few weeks was associated with little or no improvement in the clinical state of the patient or a higher mortality rate. Return to normal levels of MBP indicated a more favourable outcome of disease. Hence MBP estimation gave not only an indicator of the degree of neurological damage but also an important marker to evaluate patients' progress and response to treatment. (author)

  18. A robust, efficient and flexible method for staining myelinated axons in blocks of brain tissue.

    Science.gov (United States)

    Wahlsten, Douglas; Colbourne, Frederick; Pleus, Richard

    2003-03-15

    Previous studies have demonstrated the utility of the gold chloride method for en bloc staining of a bisected brain in mice and rats. The present study explores several variations in the method, assesses its reliability, and extends the limits of its application. We conclude that the method is very efficient, highly robust, sufficiently accurate for most purposes, and adaptable to many morphometric measures. We obtained acceptable staining of commissures in every brain, despite a wide variety of fixation methods. One-half could be stained 24 h after the brain was extracted and the other half could be stained months later. When staining failed because of an exhausted solution, the brain could be stained successfully in fresh solution. Relatively small changes were found in the sizes of commissures several weeks after initial fixation or staining. A half brain stained to reveal the mid-sagittal section could then be sectioned coronally and stained again in either gold chloride for myelin or cresyl violet for Nissl substance. Uncertainty, arising from pixelation of digitized images was far less than errors arising from human judgments about the histological limits of major commissures. Useful data for morphometric analysis were obtained by scanning the surface of a gold chloride stained block of brain with an inexpensive flatbed scanner.

  19. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen.

    Science.gov (United States)

    Ponomarenko, Natalia A; Durova, Oxana M; Vorobiev, Ivan I; Belogurov, Alexey A; Kurkova, Inna N; Petrenko, Alexander G; Telegin, Georgy B; Suchkov, Sergey V; Kiselev, Sergey L; Lagarkova, Maria A; Govorun, Vadim M; Serebryakova, Marina V; Avalle, Bérangère; Tornatore, Pete; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

    2006-01-10

    Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes "an antibody enzyme" (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP(85-101) peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibody-mediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.

  20. Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting.

    Science.gov (United States)

    Stepanov, A V; Belogurov, A A; Kothapalli, P; Shamborant, O G; Knorre, V D; Telegin, G B; Ovsepyan, A A; Ponomarenko, N A; Deyev, S M; Kaveri, S V; Gabibov, A G

    2015-01-01

    B cells play a crucial role in the development and pathogenesis of systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce antibodies, but also secrete pro-inflammatory cytokines and present specific autoantigens to T cells. The treatment of autoimmune diseases via the elimination of the majority of B cells using the monoclonal anti-CD19/20 antibody (Rituximab) causes systemic side effects and, thus, requires a major revision. Therapeutic intervention directed towards selective elimination of pathogenic autoreactive B cells has the potential to become a universal approach to the treatment of various autoimmune abnormalities. Here, we developed a recombinant immunotoxin based on the immunodominant peptide of the myelin basic protein (MBP), fused to the antibody Fc domain. We showed that the obtained immunotoxin provides selective in vivo elimination of autoreactive B cells in mice with experimental autoimmune encephalomyelitis. The proposed conception may be further used for the development of new therapeutics for a targeted treatment of multiple sclerosis and other autoimmune disorders.

  1. Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells.

    Science.gov (United States)

    Yamashita, Tomoko; Miyamoto, Yuki; Bando, Yoshio; Ono, Takashi; Kobayashi, Sakurako; Doi, Ayano; Araki, Toshihiro; Kato, Yosuke; Shirakawa, Takayuki; Suzuki, Yutaka; Yamauchi, Junji; Yoshida, Shigetaka; Sato, Naoya

    2017-01-01

    Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods. We developed a proprietary dissociated monolayer and feeder-free culture system to handle pluripotent stem cell cultures. Because the dissociated monolayer and feeder-free culture system improves the quality and growth of primate pluripotent stem cells, these cells could potentially be differentiated into any desired functional cells and consistently cultured in large-scale conditions. In the current study, oligodendrocyte progenitor cells and mature oligodendrocytes were generated within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. Moreover, it was possible to freeze, thaw, and successfully re-culture the differentiating cells. These results showed that embryonic stem cells and human induced pluripotent stem cells maintained in a

  2. Characteristics of boys with the so-called true undescended testis diagnosed at the third postnatal month--a population-based case-control study.

    Science.gov (United States)

    Mavrogenis, Stelios; Urbán, Robert; Czeizel, Andrew E

    2015-07-01

    Undescended testis (cryptorchidism) is a common congenital abnormality of male genital organs diagnosed at birth followed with frequent postnatal descensus. However, the so-called isolated true undescended testis (ITUT) diagnosed at the third postnatal month seems to be an independent defect-entity, and this hypothesis was planned to confirm or reject in the study. The evaluation of birth outcomes and maternal socio-demographic data of cases with ITUT in the population-based large dataset of the Hungarian Congenital Abnormality Registry. There was a higher rate of preterm birth and particularly of low birthweight in 2052 cases with ITUT compared to 24,814 population male controls without any defects. The rate of twins was not higher in cases with older mothers, higher birth order and lower socio-economic status. The comparison of data of boys with undescended testis diagnosed at birth found in the previous study and with ITUT in this study confirmed our hypothesis. Undescended testis can be differentiated into two subgroups: boys with frequent postnatal descensus mainly after preterm delivery and boys with ITUT without postnatal testis descensus with frequent intrauterine growth restriction, older mothers with higher birth order and low socio-economic status.

  3. Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

    Science.gov (United States)

    Murad, S; Strycharz, G D; Kishimoto, Y

    1976-09-10

    Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

  4. Targeted surveillance for postnatal hearing loss: a program evaluation.

    Science.gov (United States)

    Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

    2012-07-01

    The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

  5. Quality and uptake of antenatal and postnatal care in Haiti.

    Science.gov (United States)

    Mirkovic, Kelsey R; Lathrop, Eva; Hulland, Erin N; Jean-Louis, Reginald; Lauture, Daniel; D'Alexis, Ghislaine Desinor; Handzel, Endang; Grand-Pierre, Reynold

    2017-02-02

    Despite improvement, maternal mortality in Haiti remains high at 359/100,000 live births. Improving access to high quality antenatal and postnatal care has been shown to reduce maternal mortality and improve newborn outcomes. Little is known regarding the quality and uptake of antenatal and postnatal care among Haitian women. Exit interviews were conducted with all pregnant and postpartum women seeking care from large health facilities (n = 10) in the Nord and Nord-Est department and communes of St. Marc, Verrettes, and Petite Rivière in Haiti over the study period (March-April 2015; 3-4 days/facility). Standard questions related to demographics, previous pregnancies, current pregnancy, and services/satisfaction during the visit were asked. Total number of antenatal visits were abstracted from charts of recently delivered women (n = 1141). Provider knowledge assessments were completed by antenatal and postnatal care providers (n = 39). Frequencies were calculated for descriptive variables and multivariable logistic regression was used to explore predictors of receiving 5 out of 10 counseling messages among pregnant women. Among 894 pregnant women seeking antenatal care, most reported receiving standard clinical service components during their visit (97% were weighed, 80% had fetal heart tones checked), however fewer reported receiving recommended counseling messages (44% counselled on danger signs, 33% on postpartum family planning). Far fewer women were seeking postnatal care (n = 63) and similar service patterns were reported. Forty-three percent of pregnant women report receiving at least 5 out of 10 counseling messages. Pregnant women on a repeat visit and women with greater educational attainment had greater odds of reporting having received 5 out of 10 counseling messages (2 nd visit: adjusted odds ratio [aOR] =1.70, 95% confidence interval [CI]: 1.09-2.66; 5+ visit: aOR = 5.44, 95% CI: 2.91-10.16; elementary school certificate: a

  6. Automated brain tissue and myelin volumetry based on quantitative MR imaging with various in-plane resolutions.

    Science.gov (United States)

    Andica, C; Hagiwara, A; Hori, M; Nakazawa, M; Goto, M; Koshino, S; Kamagata, K; Kumamaru, K K; Aoki, S

    2018-05-01

    Segmented brain tissue and myelin volumes can now be automatically calculated using dedicated software (SyMRI), which is based on quantification of R 1 and R 2 relaxation rates and proton density. The aim of this study was to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions. We scanned 10 healthy subjects on a 1.5T MR scanner with in-plane resolutions of 0.8, 2.0 and 3.0mm. Two scans were performed for each resolution. The acquisition time was 7-min and 24-sec for 0.8mm, 3-min and 9-sec for 2.0mm and 1-min and 56-sec for 3.0mm resolutions. The volumes of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV) and myelin were compared between in-plane resolutions. Repeatability for each resolution was then analyzed. No significant differences in volumes measured were found between the different in-plane resolutions, except for NoN between 0.8mm and 2.0mm and between 2.0mm and 3.0mm. The repeatability error value for the WM, GM, CSF, NoN, BPV and myelin volumes relative to ICV was 0.97%, 1.01%, 0.65%, 0.86%, 1.06% and 0.25% in 0.8mm; 1.22%, 1.36%, 0.73%, 0.37%, 1.18% and 0.35% in 2.0mm and 1.18%, 1.02%, 0.96%, 0.45%, 1.36%, and 0.28% in 3.0mm resolutions. SyMRI brain tissue and myelin volumetry with low in-plane resolution and short acquisition times is robust and has a good repeatability so could be useful for follow-up studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Mode of birth and women’s psychological and physical wellbeing in the postnatal period

    Directory of Open Access Journals (Sweden)

    Rowlands Ingrid J

    2012-11-01

    Full Text Available Abstract Background Physical and psychological problems after childbirth are common, and may have a significant negative and long-term impact on women’s wellbeing and daily functioning. The method of birth may be a particularly important factor influencing women’s health and wellbeing following birth, however, population-wide evidence is limited. This study uses data from 5,332 women who responded to a national survey of women’s experiences of maternity care in England. We examined women’s postnatal wellbeing in the first three months after birth, and whether these varied by mode of birth. Methods This is a secondary analysis of survey data using a random sample of women selected from birth registration. We used multinomial logistic regression models to examine the association between women’s self-reported psychological symptoms, health problems and mode of birth. Results Women who had forceps-assisted vaginal births and unplanned caesarean section births reported the poorest health and wellbeing, while those of women who had unassisted vaginal births and planned caesarean section births were less affected by the birth process. Most women’s physical and emotional health appeared to improve with time, however, those who had a forceps-assisted vaginal birth were more likely to report ongoing posttraumatic-type symptoms several months after the birth. Conclusions Mode of birth was associated with differences in outcomes at three months. By comparison to women who had unassisted vaginal births, the risk of reduced postnatal health and wellbeing was higher amongst the women who had forceps-assisted vaginal births but not amongst women who had ventouse-assisted vaginal births. This would suggest that it is important to differentiate the different types of instrumental birth in outcome studies. Of concern was the higher rate of posttraumatic-type symptoms among women who had forceps-assisted vaginal births relative to the other modes of

  8. Barriers to utilization of postnatal care at village level in Klaten district, central Java Province, Indonesia.

    Science.gov (United States)

    Probandari, Ari; Arcita, Akhda; Kothijah, Kothijah; Pamungkasari, Eti Poncorini

    2017-08-07

    Maternal health remains a persisting public health challenge in Indonesia. Postnatal complications, in particular, are considered as maternal health problems priority that should be addressed. Conducting adequate care for postnatal complications will improve the quality of life of mothers and babies. With the universal health coverage implementation, the Indonesian government provides free maternal and child health services close to clients at the village level, which include postnatal care. Our study aimed to explore barriers to utilization of postnatal care at the village level in Klaten district, Central Java Province, Indonesia. A qualitative study was conducted in March 2015 - June 2016 in Klaten district, Central Java, Indonesia. We selected a total of 19 study participants, including eight mothers with postnatal complications, six family members, and five village midwives for in-depth interviews. We conducted a content analysis technique on verbatim transcripts of the interviews using open code software. This study found three categories of barriers to postnatal care utilization in villages: mother and family members' health literacy on postnatal care, sociocultural beliefs and practices, and health service responses. Most mothers did not have adequate knowledge and skills regarding postnatal care that reflected how they lacked awareness and practice of postnatal care. Inter-generational norms and myths hindered mothers from utilizing postnatal care and from having adequate nutritional intake during the postnatal period. Mothers and family members conducted unsafe self-treatment to address perceived minor postnatal complication. Furthermore, social power from extended family influenced the postnatal care health literacy for mother and family members. Postnatal care in the village lacked patient-centered care practices. Additionally, midwives' workloads and capacities to conduct postnatal information, education and counseling were also issues. Despite the

  9. The effectiveness of exercise as a treatment for postnatal depression: study protocol

    Directory of Open Access Journals (Sweden)

    Daley Amanda J

    2012-06-01

    Full Text Available Abstract Background Postnatal depression can have a substantial impact on the woman, the child and family as a whole. Thus, there is a need to examine different ways of helping women experiencing postnatal depression; encouraging them to exercise may be one way. A meta analysis found some support for exercise as an adjunctive treatment for postnatal depression but the methodological inadequacy of the few small studies included means that it is uncertain whether exercise reduces symptoms of postnatal depression. We aim to determine whether a pragmatic exercise intervention that involves one-to-one personalised exercise consultations and telephone support plus usual care in women with postnatal depression, is superior to usual care only, in reducing symptoms of postnatal depression. Methods We aim to recruit 208 women with postnatal depression in the West Midlands. Recently delivered women who meet the ICD-10 diagnosis for depression will be randomised to usual care plus exercise or usual care only. The exercise intervention will be delivered over 6 months. The primary outcome measure is difference in mean Edinburgh Postnatal Depression Scale score between the groups at six month follow-up. Outcome measures will be assessed at baseline and at six and 12 month post randomisation. Discussion Findings from the research will inform future clinical guidance on antenatal and postnatal mental health, as well as inform practitioners working with postnatal depression. Trial registration number ISRCTN84245563

  10. Postnatal ontogeny of limb proportions and functional indices in the subterranean rodent Ctenomys talarum (Rodentia: Ctenomyidae).

    Science.gov (United States)

    Echeverría, Alejandra Isabel; Becerra, Federico; Vassallo, Aldo Iván

    2014-08-01

    Burrow construction in the subterranean Ctenomys talarum (Rodentia: Ctenomyidae) primarily occurs by scratch-digging. In this study, we compared the limbs of an ontogenetic series of C. talarum to identify variation in bony elements related to fossorial habits using a morphometrical and biomechanical approach. Diameters and functional lengths of long bones were measured and 10 functional indices were constructed. We found that limb proportions of C. talarum undergo significant changes throughout postnatal ontogeny, and no significant differences between sexes were observed. Five of six forelimb indices and two of four hindlimb indices showed differences between ages. According to discriminant analysis, the indices that contributed most to discrimination among age groups were robustness of the humerus and ulna, relative epicondylar width, crural and brachial indices, and index of fossorial ability (IFA). Particularly, pups could be differentiated from juveniles and adults by more robust humeri and ulnae, wider epicondyles, longer middle limb elements, and a proportionally shorter olecranon. Greater robustness indicated a possible compensation for lower bone stiffness while wider epicondyles may be associated to improved effective forces in those muscles that originate onto them, compensating the lower muscular development. The gradual increase in the IFA suggested a gradual enhancement in the scratch-digging performance due to an improvement in the mechanical advantage of forearm extensors. Middle limb indices were higher in pups than in juveniles-adults, reflecting relatively more gracile limbs in their middle segments, which is in accordance with their incipient fossorial ability. In sum, our results show that in C. talarum some scratch-digging adaptations are already present during early postnatal ontogeny, which suggests that they are prenatally shaped, and other traits develop progressively. The role of early digging behavior as a factor influencing on

  11. The making of a monster: postnatal ontogenetic changes in craniomandibular shape in the great sabercat Smilodon.

    Directory of Open Access Journals (Sweden)

    Per Christiansen

    Full Text Available Derived sabercats had craniomandibular morphologies that in many respects were highly different from those of extant felids, and this has often been interpreted functionally as adaptations for predation at extreme gape angles with hypertrophied upper canines. It is unknown how much of this was a result of intraspecific postnatal ontogeny, since juveniles of sabercats are rare and no quantitative study has been made of craniomandibular ontogeny. Postnatal ontogenetic craniomandibular shape changes in two morphologically derived sabercats, Smilodon fatalis and S. populator, were analysed using geometric morphometrics and compared to three species of extant pantherines, the jaguar, tiger, and Sunda clouded leopard. Ontogenetic shape changes in Smilodon usually involved the same areas of the cranium and mandible as in extant pantherines, and large-scale modularization was similar, suggesting that such may have been the case for all felids, since it followed the same trends previously observed in other mammals. However, in other respects Smilodon differed from extant pantherines. Their crania underwent much greater and more localised ontogenetic shape changes than did the mandibles, whereas crania and mandibles of extant pantherines underwent smaller, fewer and less localised shape changes. Ontogenetic shape changes in the two species of Smilodon are largely similar, but differences are also present, notably those which may be tied to the presence of larger upper canines in S. populator. Several of the specialized cranial characters differentiating adult Smilodon from extant felids in a functional context, which are usually regarded as evolutionary adaptations for achieving high gape angles, are ontogenetic, and in several instances ontogeny appears to recapitulate phylogeny to some extent. No such ontogenetic evolutionary adaptive changes were found in the extant pantherines. Evolution in morphologically derived sabercats involved greater cranial

  12. Developmental programming of long non-coding RNAs during postnatal liver maturation in mice.

    Directory of Open Access Journals (Sweden)

    Lai Peng

    Full Text Available The liver is a vital organ with critical functions in metabolism, protein synthesis, and immune defense. Most of the liver functions are not mature at birth and many changes happen during postnatal liver development. However, it is unclear what changes occur in liver after birth, at what developmental stages they occur, and how the developmental processes are regulated. Long non-coding RNAs (lncRNAs are involved in organ development and cell differentiation. Here, we analyzed the transcriptome of lncRNAs in mouse liver from perinatal (day -2 to adult (day 60 by RNA-Sequencing, with an attempt to understand the role of lncRNAs in liver maturation. We found around 15,000 genes expressed, including about 2,000 lncRNAs. Most lncRNAs were expressed at a lower level than coding RNAs. Both coding RNAs and lncRNAs displayed three major ontogenic patterns: enriched at neonatal, adolescent, or adult stages. Neighboring coding and non-coding RNAs showed the trend to exhibit highly correlated ontogenic expression patterns. Gene ontology (GO analysis revealed that some lncRNAs enriched at neonatal ages have their neighbor protein coding genes also enriched at neonatal ages and associated with cell proliferation, immune activation related processes, tissue organization pathways, and hematopoiesis; other lncRNAs enriched at adolescent ages have their neighbor protein coding genes associated with different metabolic processes. These data reveal significant functional transition during postnatal liver development and imply the potential importance of lncRNAs in liver maturation.

  13. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    Science.gov (United States)

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. Impact of maternal and postnatal zinc dietary status on the prostate of pubescent and adult rats.

    Science.gov (United States)

    Camora, Lucas F; Silva, Ana Priscila G; Santos, Sérgio A A; Justulin, Luis A; Perobelli, Juliana E; Barbisan, Luis Fernando; Scarano, Wellerson R

    2017-11-01

    Zinc is important for cell physiology and alteration of its levels during development can modulate a series of biological events. The aim of this study was to investigate whether dietary zinc deficiency or supplementation during morphogenesis and early postnatal development could interfere in prostate maturation. Pregnant rats were exposed to a standard diet (NZ:35 mg Zn/kg chow), low-zinc diet (LZ:3 mg of Zn/kg chow) and zinc-supplemented diet (HZ:180 mg/Kg chow) from gestational day 10 (GD10) through postnatal day 21 (PND21). After weaning, male offspring were divided into three groups that were submitted to the same food conditions as their mothers until PND53. The animals were euthanized at PND53 and PND115. The ventral prostate was removed, weighed and its fragments were subjected to histological, western blot and zymography analysis. PND53: body and prostate weight were lower in LZ compared to NZ; the epithelial compartment was reduced while the stromal compartment was increased in LZ compared to NZ; there was an increase in the amount of collagen and reduction in AR and SIRT1 expression in LZ compared to NZ. PND115: body weight was lower in LZ compared to NZ and prostate weight was similar among the groups; peripheral physiological hyperplasia was observed, as well as an increased epithelial proliferation index and reduced PAR4 expression in LZ and HZ compared to NZ. Zinc deficiency during prostate morphogenesis and differentiation is potentially harmful to its morphology, however, by restoring the standard dietary environment, the gland responds to the new microenvironment independent of the previous dietary condition. © 2017 International Federation for Cell Biology.

  15. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.

    Science.gov (United States)

    Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D

    2016-02-12

    A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.

  16. Post natal use of analgesics: comparisons between conventional postnatal wards and a maternity hotel.

    Science.gov (United States)

    Nordeng, Hedvig; Eskild, Anne; Nesheim, Britt-Ingjerd

    2010-04-01

    To investigate factors related to analgesic use after delivery, and especially whether rates of analgesic use were different in a midwife-managed maternity hotel as compared to conventional postnatal wards. One maternity hotel and two conventional postnatal wards at Ullevål University Hospital in Oslo, Norway. Data were obtained from hospital records for 804 women with vaginal deliveries. Postnatal analgesic use. Overall, approximately half the women used analgesics after vaginal delivery in both conventional postnatal wards and maternity hotel. The factors that were significantly associated with use of analgesics postnatally in multivariate analysis were multiparity, having a non-Western ethnicity, smoking in pregnancy, younger age, instrumental delivery, analgesic use during labour, maternal complications post partum, and duration of postnatal stay 4 days or more. The use of analgesics is determined by socio-demographic and obstetric factors rather than the organisation of the ward.

  17. Women's experiences of postnatal distress: a qualitative study.

    Science.gov (United States)

    Coates, Rose; Ayers, Susan; de Visser, Richard

    2014-10-14

    Women can experience a range of psychological problems after birth, including anxiety, depression and adjustment disorders. However, research has predominantly focused on depression. Qualitative work on women's experiences of postnatal mental health problems has sampled women within particular diagnostic categories so not looked at the range of potential psychological problems. The aims of this study were to explore how women experienced and made sense of the range of emotional distress states in the first postnatal year. A qualitative study of 17 women who experienced psychological problems in the first year after having a baby. Semi-structured interviews took place in person (n =15) or on the telephone (n =2). Topics included women's experiences of becoming distressed and their recovery. Data were analysed using Interpretative Phenomenological Analysis (IPA). Themes were developed within each interview before identifying similar themes for multiple participants across interviews, in order to retain an idiographic approach. Psychological processes such as guilt, avoidance and adjustment difficulties were experienced across different types of distress. Women placed these in the context of defining moments of becoming a mother; giving birth and breastfeeding. Four superordinate themes were identified. Two concerned women's unwanted negative emotions and difficulties adjusting to their new role. "Living with an unwelcome beginning" describes the way mothers' new lives with their babies started out with unwelcome emotions, often in the context of birth and breastfeeding difficulties. All women spoke about the importance of their postnatal healthcare experiences in "Relationships in the healthcare system". "The shock of the new" describes women's difficulties adjusting to the demands of motherhood and women emphasised the importance of social support in "Meeting new support needs". These findings emphasise the need for exploration of psychological processes such as

  18. Postnatal medical complications and behavioral inhibition in the offspring

    Directory of Open Access Journals (Sweden)

    Eva Moehler

    2007-01-01

    Full Text Available Se ha sugerido que la inhibición conductual representa un indicador temperamental importante en la predicción del desarrollo emocional del niño, del adolescente e incluso del adulto. En consonancia, el objetivo de este estudio experimental fue investigar el impacto de las complicaciones pre-, peri-, y postnatales sobre la inhibición conductual. Se midió la inhibición conductual de niños que empiezan a andar mediante un procedimiento estandarizado de laboratorio en 101 niños con 14 meses de edad postnatal. Las complicaciones médicas fueron evaluadas a través de las Rutter Scales, tomadas por el examinador de registros médicos de las pacientes internadas, y de documentaciones sobre el embarazo en el caso de las no hospitalizadas. Los criterios de inclusión fueron un peso al nacer por encima de 2500g, 37 semanas o más de gestación y puntuaciones APGAR por encima de 7. Las complicaciones postnatales evaluadas abarcaron ictericia fisiológica, trastornos de adaptación, enfermedades contagiosas, entre otras. Las complicaciones médicas en el periodo postnatal pero no en el pre- o perinatal resultaron aumentar significativamente la inhibición conductual a los 14 meses de edad postnatal. Los esfuerzos preventivos orientados al preescolar y al desarrollo emocional del niño deberían tomar en consideración que los niños con complicaciones neonatal parecen tener un mayor riesgo de presentar trastornos de internalización en su vida posteriormente.

  19. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    International Nuclear Information System (INIS)

    Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

    2014-01-01

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  20. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Energy Technology Data Exchange (ETDEWEB)

    Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

    2014-03-15

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  1. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth

    DEFF Research Database (Denmark)

    Iszatt, N.; Stigum, H.; Verner, M. A.

    2015-01-01

    prenatal and postnatal effects. OBJECTIVES: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). METHODS: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p...... growth, and it contains state-of-the-art exposure modeling. Prenatal p,p'-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels....

  2. Determinants of postnatal care non-utilization among women in Nigeria.

    Science.gov (United States)

    Somefun, Oluwaseyi Dolapo; Ibisomi, Latifat

    2016-01-11

    Although, there are several programs in place in Nigeria to ensure maternal and child health, maternal and neonatal mortality rates remain high with maternal mortality rates being 576/100,000 and neonatal mortality rates at 37/1000 live births (NDHS, 2013). While there are many studies on the utilization of maternal health services such as antenatal care and skilled delivery at birth, studies on postnatal care are limited. Therefore, the aim of this study is to examine the factors associated with the non-utilization of postnatal care among mothers in Nigeria using the Nigeria Demographic and Health Survey (NDHS) 2013. For analysis, the postnatal care uptake for 19,418 children born in the 5 years preceding the survey was considered. The dependent variable was a composite variable derived from a list of questions on postnatal care. A multinomial logistic regression model was applied to examine the adjusted and unadjusted determinants of non-utilization of postnatal care. Results from this study showed that 63% of the mothers of the 19,418 children did not utilize postnatal care services in the period examined. About 42% of the study population between 25 and 34 years did not utilize postnatal care and 61% of the women who did not utilize postnatal care had no education. Results from multinomial logistic regression show that antenatal care use, distance, education, place of delivery, region and wealth status are significantly associated with the non-utilization of postnatal care services. This study revealed the low uptake of postnatal care service in Nigeria. To increase mothers' utilization of postnatal care services and improve maternal and child health in Nigeria, interventions should be targeted at women in remote areas who don't have access to services and developing mobile clinics. In addition, it is crucial that steps should be taken on educating women. This would have a significant influence on their perceptions about the use of postnatal care services in

  3. Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum

    DEFF Research Database (Denmark)

    Techau, Michala E.; Johansen, Maria V.; Aasted, Bent

    2007-01-01

    of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P prenatally infected animals compared to the control...... group (P prenatal group showed higher levels of TGF-beta 1 in the liver compared with the postnatally infected group (P control group (P prenatally exposed pigs.......The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed...

  4. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    Energy Technology Data Exchange (ETDEWEB)

    Ruskamo, Salla [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Yadav, Ravi P. [Banaras Hindu University, Varanasi (India); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Sharma, Satyan; Lehtimäki, Mari [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Laulumaa, Saara [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Aggarwal, Shweta; Simons, Mikael [Max Planck Institute for Experimental Medicine, Göttingen (Germany); Bürck, Jochen; Ulrich, Anne S. [Karlsruhe Institute for Technology (KIT), Karlsruhe (Germany); Juffer, André H. [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Kursula, Inari [University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Kursula, Petri, E-mail: petri.kursula@oulu.fi [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); University of Hamburg, Hamburg (Germany)

    2014-01-01

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer.

  5. Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro

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    Volker Kroehne

    2017-09-01

    Full Text Available Endogenous oligodendrocyte progenitor cells (OPCs are a promising target to improve functional recovery after spinal cord injury (SCI by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs. Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable

  6. Protracted postnatal neurogenesis and radiosensitivity in the rabbit's dentate gyrus

    International Nuclear Information System (INIS)

    Gueneau, G.; Baille, V.; Dubos, M.; Court, L.

    1986-01-01

    In the hippocampal formation of a 3-month-old rabbit submitted to a 4.5 Gy gamma irradiation a cytologic study with light and electron microscopy allowed us to make clear the dentate gyrus particular radiosensitivity as soon as the first hours after irradiation. The pycnosis lesion observed in the subgranular zone has drawn our attention in particular. We apply ourselves to describe and precise the lesion and its evolution; thanks to an autoradiographic study, we have shown its link with late postnatal neurogenesis which goes on in this zone and at last we have used the subgranular cells 'radiosensitivity as a biological test allowing to compare the various rays' effects (gamma and neutron rays). In the brain of a one-month-old monkey submitted to a 4 Gy total irradiation the same pycnotic lesion is observed: 1) in the dentate gyrus's subgranular zone and 2) in the cerebellum's outer granular layer. These two postnatal proliferative zones remain particularly sensitive to ionizing radiations. (orig.)

  7. Consequences of prenatal radiation exposure on perinatal and postnatal development

    International Nuclear Information System (INIS)

    Konermann, G.

    1982-01-01

    Acute and long-term teratogenic effects were studied in X-irradiated mice. There is evidence of a maximum susceptibility for intrauterine irradiation damage during early organogenesis with the accumulation of several processes of organ induction. Dose response curves are compared for the irradiation days 7, 10 and 13 post conceptionem based on the incidence of skeletal defects. Exposures during advanced stages of prenatal development promote the manifestation of long-term maturation defects. Corresponding postnatal phenomena and dose-relationships are described for pre- and perinatally irradiated mice. The data include late proliferative effects on liver and brain, lipid synthesis during the premyelination in brain, cerebral tigroid formation, insulin synthesis (histochemical data) in the Islands of Langerhans cells as well as disorders in the neuronal process formation. It is demonstrated that postnatal teratogenesis manifests itself as an elongated chain of interdependent processes of retardation and stabilization, the predominance of each depending on the irradiation dose and its time of application during development. In view of the generally fluctuating character of long-term maturation defects, an extended period of observation seems to be of great practical importance. (orig.)

  8. Antenatal and postnatal depression: A public health perspective

    Directory of Open Access Journals (Sweden)

    Saurabh R Shrivastava

    2015-01-01

    Full Text Available Depression is widely prevalent among women in the child-bearing age, especially during the antenatal and postnatal period. Globally, post-partum depression has been reported in almost 10% to 20% of mothers, and it can start from the moment of birth, or may result from depression evolving continuously since pregnancy. The presence of depression among women has gained a lot of attention not only because of the rising incidence or worldwide distribution, but also because of the serious negative impact on personal, family and child developmental outcomes. Realizing the importance of maternal depression on different aspects-personal, child, and familial life, there is a crucial need to design a comprehensive public health policy (including a mental health strategy, to ensure that universal psychosocial assessment in perinatal women is undertaken within the primary health care system. To conclude, depression during pregnancy and in the postnatal period is a serious public health issue, which essentially requires continuous health sector support to eventually benefit not only the woman, but also the family, the community, and health care professionals.

  9. Postnatal outcomes of prenatally diagnosed 45,X/46,XX.

    Science.gov (United States)

    Tokita, Mari J; Sybert, Virginia P

    2016-05-01

    High quality information is critical for informed decision-making in pregnancy following a prenatal diagnosis of sex chromosome aneuploidy. The goal of this study was to define the spectrum of outcomes in patients with prenatally diagnosed 45,X/46,XX mosaic Turner syndrome in order to provide a better basis for genetic counseling at the time of intrauterine diagnosis. Phenotype data for twenty-five patients with prenatally diagnosed 45,X/46,XX mosaicism were collected by retrospective chart review and, when possible, semi-structured telephone interview. Existing data from a cohort of 58 patients with postnatally diagnosed 45,X/46,XX mosaicism were used for comparison. Relative to those diagnosed postnatally, prenatal patients were more likely to have normal growth and normal secondary sexual development, less likely to manifest distinctive Turner syndrome features such as nuchal webbing and edema, and had significantly fewer renal defects. These differences underscore the need for a nuanced approach to prenatal counseling in cases of 45,X/46,XX mosaicism. © 2016 Wiley Periodicals, Inc.

  10. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

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    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  11. Prenatal and postnatal cocaine exposure predict teen cocaine use

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  12. Postnational or National Europe? European Asylum Policies and Immigration Controls

    Directory of Open Access Journals (Sweden)

    Vedrana Baričević

    2011-01-01

    Full Text Available The paper deals with the theories of the transformation of the modern functions of the nation state and the immigrant membership associated with the (legally defined status of community members exemplified by asylum policies. In the process, two fundamental approaches to the issue are distinguished: the first one emphasizing changes in the institution of the traditional national citizenship and competences of the nation state, while stressing a predominantly national character of the institution of citizenship, and the second one, which emphasizes the transformation of traditional citizenships, stressing the weakening of the role of the nation state. Therefore, in the latter case, there is increasingly more talk about postnationalism, which is a term denoting the transformation of the substantive aspects of citizenship in the EU countries. The mentioned theoretical approaches are applied to three groups of issues. First, the impact of the EU on the processes of the globalisation of the rights of asylum migrants are examined. Second, the paper works out the details of the way of formulating the policy of asylum membership in the EU member states. Third, the question of whether universal postnational inclusion of asylum migrants is at work in the EU member states, or whether the status of this group of immigrants should be found within the limits of the traditional theory of state membership and national sovereignty is addressed

  13. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Mouse models for the study of postnatal cardiac hypertrophy

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    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  15. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    Science.gov (United States)

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    contribute to the spatial differentiation of chondrocytes in the postnatal endochondral skeleton. PMID:28467498

  16. Comparison between indigenous and Western postnatal care practices in Mopani District, Limpopo Province, South Africa

    Directory of Open Access Journals (Sweden)

    Roinah N. Ngunyulu

    2015-05-01

    Full Text Available Background: Postnatal care begins immediately after the expulsion of the placenta and continues for six to eight weeks post-delivery. High standard of care is required during the postnatal period because mothers and babies are at risk and vulnerable to complications related to postpartum haemorrhage and infections. Midwives and traditional birth attendants are responsible for the provision of postnatal care in different settings, such as clinics and hospitals, and homes. Methods: A qualitative, exploratory, descriptive and contextual research approach was followed in this study. Unstructured interviews were conducted with the traditional birth attendants. An integrated literature review was conducted to identify the Western postnatalcare practices. Tesch’s process was followed during data analysis. Findings: The following main categories were identified: similarities between indigenous and Western postnatal care practices, and differences between indigenous and Western postnatal care practices. Based on these findings, training of midwives and traditional birth attendants was recommended in order to empower them with knowledge and skills regarding the indigenous and Western postnatal care practices. Conclusions: It is evident that some indigenous postnatal care practices have adverse effects on the health of postnatal women and their newborn infants, but these are unknown to the traditional birth attendants. The employment of indigenous postnatal care practices by the traditional birth attendants is also influenced by their cultural beliefs, norms, values and attitudes. Therefore, there is an urgent need to train midwives and traditional birth attendants regarding the indigenous and Western postnatal care to improve the health of postnatal women and their babies.

  17. Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

    Science.gov (United States)

    Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

    2012-12-15

    The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

  18. Staffing in postnatal units: is it adequate for the provision of quality care? Staff perspectives from a state-wide review of postnatal care in Victoria, Australia

    Directory of Open Access Journals (Sweden)

    Lumley Judith

    2006-07-01

    Full Text Available Abstract Background State-wide surveys of recent mothers conducted over the past decade in Victoria, one state of Australia, have identified that women are consistently less satisfied with the care they received in hospital following birth compared with other aspects of maternity care. Little is known of caregivers' perspectives on the provision ofhospital postnatal care: how care is organised and provided in different hospitals; what constrains the provision of postnatal care (apart from funding and what initiatives are being undertaken to improve service delivery. A state-widereview of organisational structures and processes in relation to the provision of hospital postnatal care in Victoria was undertaken. This paper focuses on the impact of staffing issues on the provision of quality postnatal care from the perspective of care providers. Methods A study of care providers from Victorian public hospitals that provide maternity services was undertaken. Datawere collected in two stages. Stage one: a structured questionnaire was sent to all public hospitals in Victoria that provided postnatal care (n = 73, exploring the structure and organisation of care (e.g. staffing, routine observations, policy framework and discharge planning. Stage two: 14 maternity units were selected and invited to participate in a more in-depth exploration of postnatal care. Thirty-eight key informant interviews were undertaken with midwives (including unit managers, associate unit managers and clinical midwives and a medical practitioner from eachselected hospital. Results Staffing was highlighted as a major factor impacting on the provision of quality postnatal care. There were significant issues associated with inadequate staff/patient ratios; staffing mix; patient mix; prioritisation of birth suites over postnatal units; and the use of non-permanent staff. Forty-three percent of hospitals reported having only midwives (i.e. no non-midwives providing postnatal care

  19. Effects of postnatal malnutrition and senescence on learning, long-term memory, and extinction in the rat.

    Science.gov (United States)

    Martínez, Yvonne; Díaz-Cintra, Sofía; León-Jacinto, Uriel; Aguilar-Vázquez, Azucena; Medina, Andrea C; Quirarte, Gina L; Prado-Alcalá, Roberto A

    2009-10-12

    There is a wealth of information indicating that the hippocampal formation is important for learning and memory consolidation. The hippocampus is very sensitive to ageing and developmentally stressful factors such as prenatal malnutrition, which produces anatomical alterations of hippocampal pyramidal cells as well as impaired spatial learning. On the other hand, there are no reports about differential effects of postnatal malnutrition, installed at birth and maintained all through life in young and aged rats, on learning and memory of active avoidance, a task with an important procedural component. We now report that learning and long-term retention of this task were impaired in young malnourished animals, but not in young control, senile control, and senile malnourished Sprague-Dawley rats; young and senile rats were 90 and 660 days of age, respectively. Extinction tests showed, however, that long-term memory of the malnourished groups and senile control animals is impaired as compared with the young control animals. These data strongly suggest that the learning and long-term retention impairments seen in the young animals were due to postnatal malnutrition; in the senile groups, this cognitive alteration did not occur, probably because ageing itself is an important factor that enables the brain to engage in compensatory mechanisms that reduce the effects of malnutrition. Nonetheless, ageing and malnutrition, conditions known to produce anatomic and functional hippocampal alterations, impede the maintenance of long-term memory, as seen during the extinction test.

  20. New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

    Directory of Open Access Journals (Sweden)

    Riyi Shi

    2013-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.

  1. Rapid whole brain myelin water content mapping without an external water standard at 1.5T.

    Science.gov (United States)

    Nguyen, Thanh D; Spincemaille, Pascal; Gauthier, Susan A; Wang, Yi

    2017-06-01

    The objective of this study is to develop rapid whole brain mapping of myelin water content (MWC) at 1.5T. The Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) pulse sequence originally developed for myelin water fraction (MWF) mapping was modified to obtain fast mapping of T1 and receiver coil sensitivity needed for MWC computation. The accuracy of the proposed T1 mapping was evaluated by comparing with the standard IR-FSE method. Numerical simulations were performed to assess the accuracy and reliability of the proposed MWC mapping. We also compared MWC values obtained with either cerebrospinal fluid (CSF) or an external water tube attached to the subject's head as the water reference. Our results from healthy volunteers show that whole brain MWC mapping is feasible in 7min and provides accurate brain T1 values. Regional brain WC and MWC measurements obtained with the internal CSF-based water standard showed excellent correlation (R>0.99) and negligible bias within narrow limits of agreement compared to those obtained with an external water standard. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

    Science.gov (United States)

    Dombrowski, Mary A.; Sasaki, Masanori; Lankford, Karen L.; Kocsis, Jeffery D.; Radtke, Christine

    2009-01-01

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

  3. Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce NOS-Driven Defects in Myelin and Vasculature

    Directory of Open Access Journals (Sweden)

    Debra A. Mayes

    2013-09-01

    Full Text Available Patients with neurofibromatosis type 1 (NF1 and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB developed, implicating a soluble mediator. Nitric oxide (NO can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1–NOS3 were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients.

  4. The human amygdaloid complex: a cytologic and histochemical atlas using Nissl, myelin, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining.

    Science.gov (United States)

    Sims, K S; Williams, R S

    1990-01-01

    We examined the distribution of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase enzyme activity in the human amygdala using histochemical techniques. Both methods revealed compartments of higher or lower enzyme activity, in cells or neuropil, which corresponded to the nuclear subdivisions of the amygdala as defined with classical Nissl and myelin methods. The boundaries between the histochemical compartments were usually so sharp that the identification of these nuclear subdivisions was enhanced. There was also variation of staining intensity within many of the nuclear subdivisions, such as the lateral and central nuclei, anterior amygdaloid area and the intercalated groups. This histochemical difference corresponded to more subtle differences in Nissl and myelin staining patterns, and suggests further structural subdivisions of potential functional significance. We present a revised scheme of anatomical parcellation of the human amygdala based upon serial analysis with all four techniques. Our expectation is that this will allow the delineation of a clearer homology between the cytoarchitectonic subdivisions of the human amygdala and those of experimental animals.

  5. Fetal adrenal gland enlargement - prenatal and postnatal management.

    Science.gov (United States)

    Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

    2017-11-01

    The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date

  6. Maternal low protein diet and postnatal high fat diet increases adipose imprinted gene expression

    Science.gov (United States)

    Maternal and postnatal diet can alter Igf2 gene expression and DNA methylation. To test whether maternal low protein and postnatal high fat (HF) diet result in alteration in Igf2 expression and obesity, we fed obese-prone Sprague-Dawley rats 8% (LP) or 20% (NP) protein for 3 wk prior to breeding and...

  7. Delayed growth, motor function and learning in preterm pigs during early postnatal life

    DEFF Research Database (Denmark)

    Andersen, Anders D.; Sangild, Per T.; Munch, Sara L.

    2016-01-01

    Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired......, and learning, relative to term pigs (all P

  8. Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

    Science.gov (United States)

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

    2011-01-01

    Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

  9. Depression in Men in the Postnatal Period and Later Child Psychology: A Population Cohort Study

    Science.gov (United States)

    Ramchandani, Paul G.; Stein, Alan; O'Connor, Thomas G.; Heron, Jon; Murray, Lynne; Evans, Jonathan

    2008-01-01

    The factors responsible for depression in men following childbirth and the association between their depression in the postnatal period and later psychiatric disorders in their children are assessed. Findings show that depression in fathers in their postnatal period is associated with later psychiatric disorders in their children, independent of…

  10. Thyroid function profile in cord blood and postnatal changes at 24 ...

    African Journals Online (AJOL)

    Background: Studying the acute postnatal changes of newborn thyroid function is essential for determining the best timing of screening for congenital hypothyroidism. There is paucity of literature on neonatal thyroid function and particularly the postnatal changes in Nigeria. Objectives: To describe the profile of thyroid ...

  11. Myosin heavy chain expression in rabbit masseter muscle during postnatal development

    NARCIS (Netherlands)

    Bredman, J. J.; Weijs, W. A.; Korfage, H. A.; Brugman, P.; Moorman, A. F.

    1992-01-01

    The expression of isoforms of myosin heavy chain (MHC) during postnatal development was studied in the masseter muscle of the rabbit. Evidence is presented that in addition to adult fast and slow myosin, the rabbit masseter contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin

  12. The postnatal progeny development of males whose sexual cells were irradiated during different stages of spermatogenesis

    International Nuclear Information System (INIS)

    Lepekhin, N.P.; Palyga, G.F.

    1995-01-01

    Distinct genetic radiosensitivity if germinal cells of males irradiated during different stages of spermatogenesis with doses of 0.25-5.0 Gy leads to reduction in vital newborn rats number in the first generation progeny and to elevated postnatal mortality rate. These postnatal ontogeny disorders depend on the irradiation dose and spermatogenesis stage for a moment irradiation. 11 refs.; 4 tabs

  13. Pre- and Postnatal Women's Leisure Time Physical Activity Patterns: A Multilevel Longitudinal Analysis

    Science.gov (United States)

    Cramp, Anita G.; Bray, Steven R.

    2009-01-01

    The purpose of this study was to examine women's leisure time physical activity (LTPA) before pregnancy, during pregnancy, and through the first 7 months postnatal. Pre- and postnatal women (n = 309) completed the 12-month Modifiable Activity Questionnaire and demographic information. Multilevel modeling was used to estimate a growth curve…

  14. The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

    2008-01-01

    Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein...... (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p...

  15. Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development

    Science.gov (United States)

    Stoffel, Wilhelm; Jenke, Britta; Blöck, Barbara; Zumbansen, Markus; Koebke, Jürgen

    2005-01-01

    Neutral sphingomyelinases sphingomyelin phosphodiesterase (SMPD)2 and -3 hydrolyze sphingomyelin to phosphocholine and ceramide. smpd2 is expressed ubiquitously, and smpd3 is expressed predominantly in neurons of the CNS. Their activation and the functions of the released ceramides have been associated with signaling pathways in cell growth, differentiation, and apoptosis. However, these cellular responses remain poorly understood. Here we describe the generation and characterization of the smpd3–/– and smpd2–/–smpd3–/– double mutant mouse, which proved to be devoid of neutral sphingomyelinase activity. SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency. Our studies suggest that SMPD3 is segregated into detergent-resistant subdomains of Golgi membranes of hypothalamic neurosecretory neurons, where its transient activation modifies the lipid bilayer, an essential step in the Golgi secretory pathway. The smpd3–/– mouse might mimic a form of human combined pituitary hormone deficiency. PMID:15764706

  16. Imaging and recording subventricular zone progenitor cells in live tissue of postnatal mice

    Directory of Open Access Journals (Sweden)

    Benjamin Lacar

    2010-07-01

    Full Text Available The subventricular zone (SVZ is one of two regions where neurogenesis persists in the postnatal brain. The SVZ, located along the lateral ventricle, is the largest neurogenic zone in the brain that contains multiple cell populations including astrocyte-like cells and neuroblasts. Neuroblasts migrate in chains to the olfactory bulb where they differentiate into interneurons. Here, we discuss the experimental approaches to record the electrophysiology of these cells and image their migration and calcium activity in acute slices. Although these techniques were in place for studying glial cells and neurons in mature networks, the SVZ raises new challenges due to the unique properties of SVZ cells, the cellular diversity, and the architecture of the region. We emphasize different methods, such as the use of transgenic mice and in vivo electroporation that permit identification of the different SVZ cell populations for patch clamp recording or imaging. Electroporation also permits genetic labeling of cells using fluorescent reporter mice and modification of the system using either RNA interference technology or floxed mice. In this review, we aim to provide conceptual and technical details of the approaches to perform electrophysiological and imaging studies of SVZ cells.

  17. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

    Science.gov (United States)

    Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

    2017-12-04

    Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

  18. PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

    Science.gov (United States)

    Zhu, Guo; Rankin, Sherri L; Larson, Jon D; Zhu, Xiaoyan; Chow, Lionel M L; Qu, Chunxu; Zhang, Jinghui; Ellison, David W; Baker, Suzanne J

    2017-01-01

    Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. The experience of seeking help for postnatal depression.

    Science.gov (United States)

    Holopainen, Debbi

    2002-01-01

    This qualitative study sought to explore women's experiences of support and treatment for postnatal depression. In-depth interviews from seven women were analysed using the phenomenological method described by Creswell (1998). Findings indicate that partners provided women the most support. The women did not know where to seek professional help, often being identified and helped by the maternal health nurse who monitors and guides the progress of their babies' development. Hospital programs were criticised for not informing and involving family. The women were dissatisfied with hospital doctors and their GPs claiming they had limited time for counselling, preferring to prescribe medication that alleviated symptoms but reinforced feelings of inadequacy. Recommendations are made to involve families and to use the unique position of the maternal health nurse in assessing new mothers.

  20. Roles of MicroRNA across Prenatal and Postnatal Periods

    Directory of Open Access Journals (Sweden)

    Ilaria Floris

    2016-11-01

    Full Text Available Communication between mother and offspring in mammals starts at implantation via the maternal–placental–fetal axis, and continues postpartum via milk targeted to the intestinal mucosa. MicroRNAs (miRNAs, short, noncoding single-stranded RNAs, of about 22 nucleotides in length, are actively involved in many developmental and physiological processes. Here we highlight the role of miRNA in the dynamic signaling that guides infant development, starting from implantation of conceptus and persisting through the prenatal and postnatal periods. miRNAs in body fluids, particularly in amniotic fluid, umbilical cord blood, and breast milk may offer new opportunities to investigate physiological and/or pathological molecular mechanisms that portend to open novel research avenues for the identification of noninvasive biomarkers.

  1. Postnatal development of plasma amino acids in hyperphagic rats.

    Science.gov (United States)

    Salvadó, M J; Segués, T; Arola, L

    1991-01-01

    The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

  2. Long-term impact of prematurity on postnatal neurohormonal regulation

    Directory of Open Access Journals (Sweden)

    M. I. Ziborova

    2016-01-01

    Full Text Available This article considers the psychophysiological and neuroendocrine differences characteristic of premature children, which are as a result of long-term perinatal consequences. Particular emphasis is laid on the effects of the hypothalamic-pituitary-adrenocortical stress system, the performance of which is reprogramed during complicated pregnancy, labor, and postnatal period under pain stress due to medical manipulations. Being extremely sensitive to all these exposures, the brain of a premature infant develops during activation of the stress system and takes on a few distinctive properties in addition to independent neuroanatomical distinctions due to premature birth. The altered neurohormonal patterns revealed in very prematurely born children and adolescents involve the regulation of mental processes, behavior, metabolism, and circadian rhythms (sleep-wake regulation, which differ from those in their maturely born peers. These cases allow learning and behavior problems and lower cognitive estimates to be considered in normally developing children born extremely prematurely who have also hormonal dysregulation.

  3. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  4. Developing electrical properties of postnatal mouse lumbar motoneurons

    Directory of Open Access Journals (Sweden)

    Jacques eDurand

    2015-09-01

    Full Text Available We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest input resistance and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained. The delayed onset firing type has the highest rheobase and the fastest action potential whereas the transient firing group has the lowest rheobase and the less mature action potential. We found 32% and 10 % of motoneurons with a transient firing at P3-P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3-P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis are the most preponderant at P6-P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis emerge at P8-P9. The emergence of type 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week

  5. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae

    2003-01-01

    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  6. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    2016-11-01

    Full Text Available Objective: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD by comparing them to their siblings without autistic disorders. Method: The present study is cross sectional and comparative. It was conducted over a period of three months (July–September 2014. It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Results: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p = 0.03 and p = 0.042. In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases, long duration of delivery and prematurity (18% of cases for each factor, while postnatal factors were represented principally by respiratory infections (24%. As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD. Resumo: Objetivo: Identificar fatores de risco pré-natal, perinatal e pós-natal em crianças com transtorno do espectro do autismo (TEA ao compará-las a irmãos sem transtornos de autismo. Método: Este estudo é transversal e comparativo. Ele foi conduzido em um per

  7. Maternal stress in pregnancy affects myelination and neurosteroid regulatory pathways in the guinea pig cerebellum.

    Science.gov (United States)

    Bennett, Greer A; Palliser, Hannah K; Shaw, Julia C; Palazzi, Kerrin L; Walker, David W; Hirst, Jonathan J

    2017-11-01

    Prenatal stress predisposes offspring to behavioral pathologies. These may be attributed to effects on cerebellar neurosteroids and GABAergic inhibitory signaling, which can be linked to hyperactivity disorders. The aims were to determine the effect of prenatal stress on markers of cerebellar development, a key enzyme in neurosteroid synthesis and the expression of GABA A receptor (GABA A R) subunits involved in neurosteroid signaling. We used a model of prenatal stress (strobe light exposure, 2 h on gestational day 50, 55, 60 and 65) in guinea pigs, in which we have characterized anxiety and neophobic behavioral outcomes. The cerebellum and plasma were collected from control and prenatally stressed offspring at term (control fetus: n = 9 male, n = 7 female; stressed fetus: n = 7 male, n = 8 female) and postnatal day (PND) 21 (control: n = 8 male, n = 8 female; stressed: n = 9 male, n = 6 female). We found that term female offspring exposed to prenatal stress showed decreased expression of mature oligodendrocytes (∼40% reduction) and these deficits improved to control levels by PND21. Reactive astrocyte expression was lower (∼40% reduction) following prenatal stress. GABA A R subunit (δ and α6) expression and circulating allopregnanolone concentrations were not affected by prenatal stress. Prenatal stress increased expression (∼150-250% increase) of 5α-reductase type-1 mRNA in the cerebellum, which may be a neuroprotective response to promote GABAergic inhibition and aid in repair. These observations indicate that prenatal stress exposure has marked effects on the development of the cerebellum. These findings suggest cerebellar changes after prenatal stress may contribute to adverse behavioral outcomes after exposure to these stresses.

  8. Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

    Science.gov (United States)

    KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

    2016-03-01

    Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

  9. A statewide review of postnatal care in private hospitals in Victoria, Australia

    Directory of Open Access Journals (Sweden)

    Forster Della A

    2010-05-01

    Full Text Available Abstract Background Concerns have been raised in Australia and internationally regarding the quality and effectiveness of hospital postnatal care, although Australian women receiving postnatal care in the private maternity sector rate their satisfaction with care more highly than women receiving public maternity care. In Victoria, Australia, two-thirds of women receive their maternity care in the public sector and the remainder in private health care sector. A statewide review of public hospital postnatal care in Victoria from the perspective of care providers found many barriers to care provision including the busyness of postnatal wards, inadequate staffing and priority being given to other episodes of care; however the study did not include private hospitals. The aim of this study was replicate the review in the private sector, to explore the structure and organisation of postnatal care in private hospitals and identify those aspects of care potentially impacting on women's experiences and maternal and infant care. This provides a more complete overview of the organisational structures and processes in postnatal care in all Victorian hospitals from the perspective of care providers. Methods A mixed method design was used. A structured postal survey was sent to all Victorian private hospitals (n = 19 and key informant interviews were undertaken with selected clinical midwives, maternity unit managers and obstetricians (n = 11. Survey data were analysed using descriptive statistics and interview data analysed thematically. Results Private hospital care providers report that postnatal care is provided in very busy environments, and that meeting the aims of postnatal care (breastfeeding support, education of parents and facilitating rest and recovery for women following birth was difficult in the context of increased acuity of postnatal care; prioritising of other areas over postnatal care; high midwife-to-woman ratios; and the number and

  10. [The study of developmental pharmacology (I). Effect of pentazocine HCl on the physiology of rats given the drug during perinatal and postnatal periods (author's transl)].

    Science.gov (United States)

    Fukawa, K; Sawabe, T; Kawano, O; Hatanaka, Y

    1978-01-01

    The effects of drug administration on the dams (F0) and their offspring (F1), particularly on the central nervous and reproductive functions of F1, were studied by oral administration of pentazocine HCl to rats during the perinatal and postnatal periods. No significant differences were observed between administered and control rats regarding body weight changes and food intake during perinatal and postnatal periods in F0 at all dosages, but temporary salivation was observed in the 200 and 100 mg/kg groups, and decline of spontaneous activity and respiratory rate, disappearance of righting reflex, clonic convulsion were observed in some of the 200 mg/kg group. No significant differences were observed regarding litter size, birth rate, state and timing of differentiation as postnatal development, sex maturity, reproductive function in F1, although some groups were slightly inferior in body weight at birth and during the nursing period. Furthermore, no differences were observed in respect to the nervous functions of balance, exercise and psychotic related activity in the open-field test.

  11. Maternal Postnatal Depression and Anxiety and Their Association with Child Emotional Negativity and Behavior Problems at Two Years

    Science.gov (United States)

    Prenoveau, Jason M.; Craske, Michelle G.; West, Valerie; Giannakakis, Andreas; Zioga, Maria; Lehtonen, Annukka; Davies, Beverley; Netsi, Elena; Cardy, Jessica; Cooper, Peter; Murray, Lynne; Stein, Alan

    2017-01-01

    Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major…

  12. Intercellular signaling pathways active during and after growth and differentiation of the lumbar vertebral growth plate.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2011-06-15

    Vertebral growth plates at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the major signaling pathways active in the postnatal mouse lumbar vertebral growth plate. The growth of all long bones is known to occur by cartilaginous growth plates. The growth plate is composed of layers of chondrocyets that actively proliferate, differentiate, die and, are replaced by bone. The role of major cell signaling pathways has been suggested for regulation of the fetal long bones. But not much is known about the molecular or cellular signals that control the postnatal vertebral growth plate and hence postnatal vertebral bone growth. Understanding such molecular mechanisms will help design therapeutic treatments for vertebral growth disorders such as scoliosis. Antibodies against activated downstream intermediates were used to identify cells in the growth plate responding to BMP, TGFβ, and FGF in cryosections of lumbar vertebrae from different postnatal age mice to identify the zones that were responding to these signals. Reporter mice were used to identify the chondrocytes responding to hedgehog (Ihh), and Wnt signaling. We present a spatial/temporal map of these signaling pathways during growth, and differentiation of the mouse lumbar vertebral growth plate. During growth and differentiation of the vertebral growth plate, its different components respond at different times to differ