WorldWideScience

Sample records for adult subventricular zone

  1. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone.

    Science.gov (United States)

    Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L; Rincon-Torroella, Jordina; Rigamonti, Daniele; García-Verdugo, Jose M; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2014-11-01

    Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n=18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age>18years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the subventricular

  2. RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres

    DEFF Research Database (Denmark)

    Popa, Natalia; Cédile, Oriane; Pollet-Villard, Xavier

    2011-01-01

    playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression......, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here...... an unexpected role of RAE-1 in regulating adult SVZ neurogenesis by supporting stem/progenitor cells proliferation....

  3. Chromatin-based epigenetics of adult subventricular zone neural stem cells

    Directory of Open Access Journals (Sweden)

    Gabriel eGonzales-Roybal

    2013-10-01

    Full Text Available In specific regions of the adult mammalian brain, neural stem cells (NSCs generate new neurons throughout life. Emerging evidence indicate that chromatin-based transcriptional regulation is a key epigenetic mechanism for the life-long function of adult NSCs. In the adult mouse brain, NSCs in the subventricular zone (SVZ retain the ability to produce both neurons and glia for the life of the animal. In this review, we discuss the origin and function of SVZ NSCs as they relate to key epigenetic concepts of development and potential underlying mechanism of chromatin-based transcriptional regulation. A central point of discussion is how SVZ NSCs – which possess many characteristics of mature, non-neurogenic astrocytes – maintain a youthful ability to produce both neuronal and glial lineages. In addition to reviewing data regarding the function of chromatin-modifying factors in SVZ neurogenesis, we incorporate our growing understanding that long noncoding RNAs (lncRNAs serve as an important element to chromatin-based transcriptional regulation, including that of SVZ NSCs. Discoveries regarding the epigenetic mechanisms of adult SVZ NSCs may provide key insights into fundamental principles of adult stem cell biology as well as the more complex and dynamic developmental environment of the embryonic brain.

  4. Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone

    Directory of Open Access Journals (Sweden)

    Mathieu Daynac

    2016-10-01

    Full Text Available Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ, one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ. The pool of non-neurogenic astrocytes was not modified, whereas the activated NSC pool increased after a short period, before progressively becoming exhausted. We also showed that Sonic Hedgehog regulates proliferation of activated NSCs in vivo and shortens both their G1 and S-G2/M phases in culture. These data demonstrate that Hh orchestrates the balance between quiescent and activated NSCs, with important implications for understanding adult neurogenesis under normal homeostatic conditions or during injury.

  5. Phosphodiesterase7 Inhibition Activates Adult Neurogenesis in Hippocampus and Subventricular Zone In Vitro and In Vivo.

    Science.gov (United States)

    Morales-Garcia, Jose A; Echeverry-Alzate, Victor; Alonso-Gil, Sandra; Sanz-SanCristobal, Marina; Lopez-Moreno, Jose A; Gil, Carmen; Martinez, Ana; Santos, Angel; Perez-Castillo, Ana

    2017-02-01

    The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cyclic adenosine 3',5'-monophosphate in the immune and central nervous system. We have previously shown that inhibitors of this enzyme are potent neuroprotective and anti-inflammatory agents. In addition, we also demonstrated that PDE7 inhibition induces endogenous neuroregenerative processes toward a dopaminergic phenotype. Here, we show that PDE7 inhibition controls stem cell expansion in the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain. Neurospheres cultures obtained from SGZ and SVZ of adult rats treated with PDE7 inhibitors presented an increased proliferation and neuronal differentiation compared to control cultures. PDE7 inhibitors treatment of neurospheres cultures also resulted in an increase of the levels of phosphorylated cAMP response element binding protein, suggesting that their effects were indeed mediated through the activation of the cAMP/PKA signaling pathway. In addition, adult rats orally treated with S14, a specific inhibitor of PDE7, presented elevated numbers of proliferating progenitor cells, and migrating precursors in the SGZ and the SVZ. Moreover, long-term treatment with this PDE7 inhibitor shows a significant increase in newly generated neurons in the olfactory bulb and the hippocampus. Also a better performance in memory tests was observed in S14 treated rats, suggesting a functional relevance for the S14-induced increase in SGZ neurogenesis. Taken together, our results indicate for the first time that inhibition of PDE7 directly regulates proliferation, migration and differentiation of neural stem cells, improving spatial learning and memory tasks. Stem Cells 2017;35:458-472.

  6. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner.

  7. Adult neural stem cells from the subventricular zone: a review of the neurosphere assay.

    Science.gov (United States)

    Gil-Perotín, Sara; Duran-Moreno, María; Cebrián-Silla, Arantxa; Ramírez, Mónica; García-Belda, Paula; García-Verdugo, José Manuel

    2013-09-01

    The possibility of obtaining large numbers of cells with potential to become functional neurons implies a great advance in regenerative medicine. A source of cells for therapy is the subventricular zone (SVZ) where adult neural stem cells (NSCs) retain the ability to proliferate, self-renew, and differentiate into several mature cell types. The neurosphere assay, a method to isolate, maintain, and expand these cells has been extensively utilized by research groups to analyze the biological properties of aNSCs and to graft into injured brains from animal models. In this review we briefly describe the neurosphere assay and its limitations, the methods to optimize culture conditions, the identity and the morphology of aNSC-derived neurospheres (including new ultrastructural data). The controversy regarding the identity and "stemness" of cells within the neurosphere is revised. The fine morphology of neurospheres, described thoroughly, allows for phenotypical characterization of cells in the neurospheres and may reveal slight changes that indirectly inform about cell integrity, cell damage, or oncogenic transformation. Along this review we largely highlight the critical points that researchers have to keep in mind before extrapolating results or translating experimental transplantation of neurosphere-derived cells to the clinical setting.

  8. A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

    Science.gov (United States)

    Vergni, Davide; Castiglione, Filippo; Briani, Maya; Middei, Silvia; Alberdi, Elena; Reymann, Klaus G.; Natalini, Roberto; Volonté, Cinzia; Matute, Carlos; Cavaliere, Fabio

    2009-01-01

    We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies. PMID:19390597

  9. A model of ischemia-induced neuroblast activation in the adult subventricular zone.

    Directory of Open Access Journals (Sweden)

    Davide Vergni

    Full Text Available We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6-24 hours, neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days, they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours. The process is further enhanced by elevating the production of the chemoattractant SDf-1alpha and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies.

  10. P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone.

    Science.gov (United States)

    Messemer, Nanette; Kunert, Christin; Grohmann, Marcus; Sobottka, Helga; Nieber, Karen; Zimmermann, Herbert; Franke, Heike; Nörenberg, Wolfgang; Straub, Isabelle; Schaefer, Michael; Riedel, Thomas; Illes, Peter; Rubini, Patrizia

    2013-10-01

    Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular zone (SVZ). Whole-cell patch-clamp recordings showed a marked potentiation of the inward current responses both to ATP and the prototypic P2X7 receptor agonist dibenzoyl-ATP (Bz-ATP) at low Ca(2+) and zero Mg(2+) concentrations in the bath medium. The Bz-ATP-induced currents reversed their polarity near 0 mV; in NPCs prepared from P2X7(-/-) mice, Bz-ATP failed to elicit membrane currents. The general P2X/P2Y receptor antagonist PPADS and the P2X7 selective antagonists Brilliant Blue G and A-438079 strongly depressed the effect of Bz-ATP. Long-lasting application of Bz-ATP induced an initial current, which slowly increased to a steady-state response. In combination with the determination of YO-PRO uptake, these experiments suggest the dilation of a receptor-channel and/or the recruitment of a dye-uptake pathway. Ca(2+)-imaging by means of Fura-2 revealed that in a Mg(2+)-deficient bath medium Bz-ATP causes [Ca(2+)](i) transients fully depending on the presence of external Ca(2+). The MTT test indicated a concentration-dependent decrease in cell viability by Bz-ATP treatment. Correspondingly, Bz-ATP led to an increase in active caspase 3 immunoreactivity, indicating a P2X7-controlled apoptosis. In acute SVZ brain slices of transgenic Tg(nestin/EGFP) mice, patch-clamp recordings identified P2X7 receptors at NPCs with pharmacological properties identical to those of their cultured counterparts. We suggest that the apoptotic/necrotic P2X7 receptors at NPCs may be of particular relevance during pathological conditions which lead to increased ATP release and thus could counterbalance the ensuing excessive cell proliferation.

  11. Subventricular zone microglia transcriptional networks.

    Science.gov (United States)

    Starossom, Sarah C; Imitola, Jaime; Wang, Yue; Cao, Li; Khoury, Samia J

    2011-07-01

    Microglia play an important role in inflammatory diseases of the central nervous system. There is evidence of microglial diversity with distinct phenotypes exhibiting either neuroprotection and repair or neurotoxicity. However the precise molecular mechanisms underlying this diversity are still unknown. Using a model of experimental autoimmune encephalomyelitis (EAE) we performed transcriptional profiling of isolated subventricular zone microglia from the acute and chronic disease phases of EAE. We found that microglia exhibit disease phase specific gene expression signatures, that correspond to unique gene ontology functions and genomic networks. Our data demonstrate for the first time, distinct transcriptional networks of microglia activation in vivo, that suggests a role as mediators of injury or repair.

  12. Subcellular distribution of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells within subventricular zone of adult rats

    Institute of Scientific and Technical Information of China (English)

    Zhining Li; Wenlong Lü; Hongyan Dong; Hongbin Fan; Ruiguo Dong; Tiejun Xu

    2011-01-01

    The subcellular localization of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyl-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.

  13. The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis.

    Science.gov (United States)

    Lim, Daniel A; Alvarez-Buylla, Arturo

    2016-05-02

    A large population of neural stem/precursor cells (NSCs) persists in the ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell-intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors.

  14. Isolation of neural progenitor cells from the human adult subventricular zone based on expression of the cell surface marker CD271

    NARCIS (Netherlands)

    van Strien, Miriam E; Sluijs, Jacqueline A; Reynolds, Brent A; Steindler, Dennis A; Aronica, Eleonora; Hol, Elly M

    2014-01-01

    Neural progenitor cells (NPCs) in the subventricular zone (SVZ) hold promise for future therapy for neurodegenerative disorders, because the stimulation of adult neurogenesis could potentially restore the function of degenerating neurons and glia. To obtain more knowledge on these NPCs, we developed

  15. Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.

    Science.gov (United States)

    Lindberg, Olle R; Brederlau, Anke; Kuhn, H Georg

    2014-04-01

    One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  16. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

    Institute of Scientific and Technical Information of China (English)

    Congmin Wang; Qiangqiang Zhang; Yue Zhang; Rui Chen; Hongjun Song; Zhengang Yang; Fang Liu; Ying-Ying Liu; Cai-Hong Zhao; Yan You; Lei Wang; Jingxiao Zhang; Bin Wei; Tong Ma

    2011-01-01

    It is of great interest to identify new neurons in the adult human brain,but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial.In the present study,we have described the general configuration of the RMS in adult monkey,fetal human and adult human brains.We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain.The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin,polysialylated neural cell adhesion molecule and βI-tubulin.Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS,indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ.Interestingly,no neuroblasts are found in the adult human olfactory bulb.Taken together,our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.

  17. Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

    Science.gov (United States)

    Wang, Congmin; You, Yan; Qi, Dashi; Zhou, Xing; Wang, Lei; Wei, Song; Zhang, Zhuangzhi; Huang, Weixi; Liu, Zhidong; Liu, Fang; Ma, Lan; Yang, Zhengang

    2014-08-13

    In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.

  18. Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats.

    Science.gov (United States)

    Galvão, Rui P; Garcia-Verdugo, José Manuel; Alvarez-Buylla, Arturo

    2008-12-10

    In rodents, the adult subventricular zone (SVZ) generates neuroblasts which migrate to the olfactory bulb (OB) and differentiate into interneurons. Recent work suggests that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) can enhance adult SVZ neurogenesis, but the mechanism by which it acts is unknown. Here, we analyzed the role of BDNF and its receptor TrkB in adult SVZ neurogenesis. We found that TrkB is the most prominent neurotrophin receptor in the mouse SVZ, but only the truncated, kinase-negative isoform (TrkB-TR) was detected. TrkB-TR is expressed in SVZ astrocytes and ependymal cells, but not in neuroblasts. TrkB mutants have reduced SVZ proliferation and survival and fewer new OB neurons. To test whether this effect is cell-autonomous, we grafted SVZ cells from TrkB knock-out mice (TrkB-KO) into the SVZ of wild-type mice (WT). Grafted progenitors generated neuroblasts that migrated to the OB in the absence of TrkB. The survival and differentiation of granular interneurons and Calbindin(+) periglomerular interneurons seemed unaffected by the loss of TrkB, whereas dopaminergic periglomerular neurons were reduced. Intra-ventricular infusion of BDNF yielded different results depending on the animal species, having no effect on neuron production from mouse SVZ, while decreasing it in rats. Interestingly, mice and rats also differ in their expression of the neurotrophin receptor p75. Our results indicate that TrkB is not essential for adult SVZ neurogenesis and do not support the current view that delivering BDNF to the SVZ can enhance adult neurogenesis.

  19. Epidermal Growth Factor Treatment of the Adult Brain Subventricular Zone Leads to Focal Microglia/Macrophage Accumulation and Angiogenesis

    Directory of Open Access Journals (Sweden)

    Olle R. Lindberg

    2014-04-01

    Full Text Available One of the major components of the subventricular zone (SVZ neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  20. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia.

    Science.gov (United States)

    Tan, S; Zhi, P K; Luo, Z K; Shi, J

    2015-09-10

    Accumulated evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to stroke outcome. However, it is unclear whether hyperglycemia, which is frequently tested positive in patients with acute ischemic stroke, influences stroke-induced neurogenesis. The aim of the present study is to examine the effect of hyperglycemia on stroke-induced neurogenesis in a rat model of transient focal cerebral ischemia. For this purpose, adult male Sprague-Dawley rats (220-250 g) were subjected to 90 min of middle cerebral artery occlusion (MCAO). Glucose was administered during ischemia to produce target blood levels ranging from 4.83 ± 0.94 mM (normoglycemia) to 20.76 ± 1.56 mM. To label proliferating cells in ischemic ipsilateral subventricular zone (SVZ) of lateral ventricles, 5'-bromo-2'-deoxyuridine (BrdU) was injected 24h after MCAO. Brains were harvested 2h post-BrdU to evaluate the effects of hyperglycemia on infarct volume and SVZ cell proliferation. Rats that were severely hyperglycemic (19.26 ± 1.48 mM to 20.76 ± 1.56 mM) during ischemia had 24.26% increase in infarct volume (Phyperglycemia (9.43 ± 1.39-10.13 ± 1.24 mM). Our findings indicate that severe instead of mild hyperglycemia exacerbates ischemic injury and inhibits stroke-induced SVZ neurogenesis by a mechanism involving suppression of CREB and BDNF signaling.

  1. Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice.

    Science.gov (United States)

    Mastrorilli, Valentina; Scopa, Chiara; Saraulli, Daniele; Costanzi, Marco; Scardigli, Raffaella; Rouault, Jean-Pierre; Farioli-Vecchioli, Stefano; Tirone, Felice

    2017-02-28

    Adult neurogenesis occurs throughout life in the dentate gyrus (DG) and the subventricular zone (SVZ), where glia-like stem cells generate new neurons. Voluntary running is a powerful neurogenic stimulus triggering the proliferation of progenitor cells in the DG but, apparently, not in the SVZ. The antiproliferative gene Btg1 maintains the quiescence of DG and SVZ stem cells. Its ablation causes intense proliferation of DG and SVZ stem/progenitor cells in young mice, followed, during adulthood, by progressive decrease of the proliferative capacity. We have previously observed that running can rescue the deficit of DG Btg1-null neurogenesis. Here, we show that in adult Btg1-null SVZ stem and neuroblast cells, the reduction of proliferation is associated with a longer cell cycle and a more frequent entry into quiescence. Notably, running increases proliferation in Btg1-null SVZ stem cells highly above the levels of sedentary wild-type mice and restores normal values of cell cycle length and quiescence in stem and neuroblast cells, without affecting wild-type cells. Btg1-null SVZ neuroblasts show also increased migration throughout the rostral migratory stream and a deficiency of differentiated neurons in the olfactory bulb, possibly a consequence of premature exit from the cycle; running, however, normalizes migration and differentiation, increasing newborn neurons recruited to the olfactory circuitry. Furthermore, running increases the self-renewal of Btg1-null SVZ-derived neurospheres and, remarkably, in aged Btg1-null mice almost doubles the proliferating SVZ stem cells. Altogether, this reveals that SVZ stem cells are endowed with a hidden supply of self-renewal capacity, coupled to cell cycle acceleration and emerging after ablation of the quiescence-maintaining Btg1 gene and following exercise.

  2. Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+/nestin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+/nestin+ cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was es...

  3. EFFECTS OF CEREBRAL CORTICAL CONCIS ON CELL PROLIFERATION OF THE SUBVENTRICULAR ZONE IN ADULT RATS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Mechanical injuries to the external regions ofthe brain including the cerebral cortex and otherparts of the telencephalon are common yet relativelyuntreatable[1].The predicament in recovery frombrain injury is that the adult central nervous systemis generally thought to be incapable of replacingdead neurons.As the SVZis nowknownto be neu-rogenic andis in close proxi mitytothe cerebral cor-tex and other functionally i mportant forebrain nu-clei,hope has risen that its neurogenesis may be co-opted for repair[...

  4. EFFECTS OF CEREBRAL CORTICAL CONCIS ON CELL PROLIFERATION OF THE SUBVENTRICULAR ZONE IN ADULT RATS

    Institute of Scientific and Technical Information of China (English)

    Zhang Yuelin; Qiu Shudong; Zhang Pengbo; Shi Wei

    2006-01-01

    Objective To investigate the proliferative response and time course of endogenous neural stem/progenitor cells after cerebral cortical concis in the adult rats. Methods Eighty adult male Sprague-Dawley rats were used in this study. Cumulative BrdU labeling was employed to detect the proliferating cells. At 1 d, 3 d, 7 d, 14 d, and 21 d after cerebral cortical concis, the rats were killed for BrdU immunohistochemical staining and cell counting in the injured ipsilateral SVZ. Results Little BrdU immunoreactivity cells was present in SVZ of the control rats from day 7 to day 21 after sham operation. The number of BrdU immunoreactivity cells in the injured ipsilateral SVZ increased at day 1 and peaked at day 7 after cerebral cortical concis. Conclusion After cerebral cortical concis of the adult rats, neural stem/progenitor cells in the injured ipsilateral SVZ markedly proliferated with a peak at day 7. This finding may be important for manipulating SVZ cells to promote the recovery from cerebral cortical concis.

  5. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate.

  6. A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

    Science.gov (United States)

    Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

    2016-01-01

    Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models.

  7. Chemokines influence the migration and fate of neural precursor cells from the young adult and middle-aged rat subventricular zone.

    Science.gov (United States)

    Gordon, R J; Mehrabi, N F; Maucksch, C; Connor, B

    2012-01-01

    We have previously demonstrated a role for the chemokines MCP-1, MIP-1α and GRO-α in directing subventricular zone (SVZ)-derived neural precursor cell migration towards the site of cell death in the adult rodent brain. However the influence of chemokines such as MCP-1, MIP-1α and GRO-α on the differentiation of adult neural precursor cells has not previously been investigated. Further, as the majority of neurological disorders and injuries occur during ageing, it is important to investigate the effect of chemokines on adult neural precursor cell cultures obtained from the ageing brain. This study therefore examined the effect of MCP-1, MIP-1α and GRO-α on SVZ-derived neural precursor cell differentiation in vitro, and assessed whether precursor cells from the middle-aged rat brain (13 months old) follow the same migratory and differential profile as neural precursor cells obtained from the young adult rat brain (2 months old). We observed that each of the chemokines examined generated differing effects in regards to neuronal or glial differentiation. Further, both MIP-1α and GRO-α increased total cell number, suggesting an effect on precursor cell proliferation and/or survival. In agreement with cultures obtained from young adult brains, SVZ-derived neural precursor cells cultured from the middle-aged brain exhibited chemotactic migration in response to a concentration gradient. These results indicate that the chemokines MCP-1, MIP-1α and GRO-α can influence both the migration and fate choice of SVZ-derived neural precursor cells, as well as promoting cell viability. While a response to each of these chemokines is maintained in the middle-aged brain, a distinct age-related alteration in differential fate can be identified.

  8. Implications of irradiating the subventricular zone stem cell niche

    Directory of Open Access Journals (Sweden)

    Vivian Capilla-Gonzalez

    2016-03-01

    Full Text Available Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.

  9. Implications of irradiating the subventricular zone stem cell niche.

    Science.gov (United States)

    Capilla-Gonzalez, Vivian; Bonsu, Janice M; Redmond, Kristin J; Garcia-Verdugo, Jose Manuel; Quiñones-Hinojosa, Alfredo

    2016-03-01

    Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs) reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.

  10. Subventricular zone cell migration: lessons from quantitative 2-photon microscopy

    Directory of Open Access Journals (Sweden)

    Rachel eJames

    2011-03-01

    Full Text Available Neuroblasts born in the adult subventricular zone (SVZ migrate long distances in the rostral migratory stream (RMS to the olfactory bulbs where they integrate into circuitry as functional interneurons. As very little was known about the dynamic parameters of SVZ neuroblast migration, we used two-photon time-lapse microscopy to analyze migration in acute slices. This involved analyzing 3-dimensional stacks of images over time and uncovered several novel aspects of SVZ migration: chains remain stable, cells can be immotile for extensive periods, morphology does not necessarily correlate with motility, neuroblasts exhibit local exploratory motility, dorsoventral migration occurs throughout the striatal SVZ and neuroblasts turn at distinctive angles. We investigated these novel findings in the SVZ and RMS from the population to the single cell level. In this review we also discuss some technical considerations when setting up a two-photon microscopic imaging system. Throughout the review we identify several unsolved questions about SVZ neuroblast migration that might be addressed with current or emerging techniques.

  11. Schisandrin A and B affect subventricular zone neurogenesis in mouse.

    Science.gov (United States)

    Sun, Yi-Xue; Cong, Yan-Long; Liu, Yang; Jin, Bo; Si, Lu; Wang, Ai-Bing; Cai, Huan; Che, Guan-Yu; Tang, Bo; Wang, Chun-Feng; Li, Zi-Yi; Zhang, Xue-Ming

    2014-10-05

    Schisandrin A and B (Sch A and B) are the main effective components extracted from the oriental medicine Schisandra chinensis which is traditionally used to enhance mental and intellectual function. Although their neuroprotective effects have been demonstrated, their influences on neurogenesis are still unknown. In the brain, new neural cells born in the subventricular zone (SVZ) next to the lateral ventricles migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB). To investigate the effects of Sch A and B on neurogenesis in the SVZ-RMS-OB system, Sch A and B were intragastrically administrated at dosages of 1, 10 and 20 mg/kg d respectively. The dose of 10 mg/kg d was selected for further analysis based on the preliminary analysis. In the SVZ, significant increases of phosphohistone H3 positive proliferating cells and the intensity of glial fibrillary acidic protein (GFAP+) cells were noticed in Sch B group. In the RMS, Sch A treatment augmented the intensity of doublecortin positive neuroblasts. In the OB, Sch A decreased tyrosine hydroxylase cells and Calbindin (CalB+) cells, while Sch B increased CalB+ cells and Calretinin (CalR+) cells. These results suggest that Sch B stimulates SVZ proliferation by enhancing GFAP+ cells and improves the survival of OB interneurons, while Sch A promotes neuroblast formation in the RMS but impairs the survival of OB interneurons. The present study provides the first evidence that Sch B exerts neuroprotective functions by enhancing neurogenesis, but Sch A mainly negatively regulates neurogenesis, in the adult SVZ-RMS-OB system.

  12. The outer subventricular zone and primate-specific cortical complexification.

    Science.gov (United States)

    Dehay, Colette; Kennedy, Henry; Kosik, Kenneth S

    2015-02-18

    Evolutionary expansion and complexification of the primate cerebral cortex are largely linked to the emergence of the outer subventricular zone (OSVZ), a uniquely structured germinal zone that generates the expanded primate supragranular layers. The primate OSVZ departs from rodent germinal zones in that it includes a higher diversity of precursor types, inter-related in bidirectional non-hierarchical lineages. In addition, primate-specific regulatory mechanisms are operating in primate cortical precursors via the occurrence of novel miRNAs. Here, we propose that the origin and evolutionary importance of the OSVZ is related to genetic changes in multiple regulatory loops and that cell-cycle regulation is a favored target for evolutionary adaptation of the cortex.

  13. Neuropeptide y promotes neurogenesis in murine subventricular zone

    DEFF Research Database (Denmark)

    Agasse, Fabienne; Bernardino, Liliana; Christiansen, Søren H

    2008-01-01

    Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We...... describe that NPY promotes SVZ neurogenesis. NPY (1 microM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ......-Jun-NH(2)-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy. Disclosure of potential conflicts of interest is found at the end of this article....

  14. Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?

    Directory of Open Access Journals (Sweden)

    Sara eXapelli

    2014-02-01

    Full Text Available Neural stem cells (NSCs from the subventricular zone (SVZ have been indicated as a source of new oligodendrocytes to use in regenerative medicine for myelin pathologies. Indeed, NSCs are multipotent cells that can self-renew and differentiate into all neural cell types of the central nervous system (CNS. In normal conditions, SVZ cells are poorly oligodendrogenic, nevertheless their oligodendrogenic potential is boosted following demyelination. Importantly, progressive restriction into the oligodendrocyte fate is specified by extrinsic and intrinsic factors, endocannabinoids being one of these factors. Although a role for endocannabinoids in oligodendrogenesis has already been foreseen, selective agonists and antagonists of cannabinoids receptors produce severe adverse side effects. Herein, we show that hemopressin, a modulator of CB1 receptors, increased oligodendroglial differentiation in SVZ neural stem/progenitor cell cultures derived from neonatal mice. The original results presented in this work suggest that hemopressin and derivatives may be of potential interest for the development of future strategies to treat demyelinating diseases.

  15. Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum.

    Science.gov (United States)

    Sullivan, Genevieve M; Mierzwa, Amanda J; Kijpaisalratana, Naruchorn; Tang, Haiying; Wang, Yong; Song, Sheng-Kwei; Selwyn, Reed; Armstrong, Regina C

    2013-12-01

    Traumatic brain injury frequently causes traumatic axonal injury (TAI) in white matter tracts. Experimental TAI in the corpus callosum of adult mice was used to examine the effects on oligodendrocyte lineage cells and myelin in conjunction with neuroimaging. The injury targeted the corpus callosum over the subventricular zone, a source of neural stem/progenitor cells. Traumatic axonal injury was produced in the rostral body of the corpus callosum by impact onto the skull at the bregma. During the first week after injury, magnetic resonance diffusion tensor imaging showed that axial diffusivity decreased in the corpus callosum and that corresponding regions exhibited significant axon damage accompanied by hypertrophic microglia and reactive astrocytes. Oligodendrocyte progenitor proliferation increased in the subventricular zone and corpus callosum. Oligodendrocytes in the corpus callosum shifted toward upregulation of myelin gene transcription. Plp/CreER(T):R26IAP reporter mice showed normal reporter labeling of myelin sheaths 0 to 2 days after injury but labeling was increased between 2 and 7 days after injury. Electron microscopy revealed axon degeneration, demyelination, and redundant myelin figures. These findings expand the cell types and responses to white matter injuries that inform diffusion tensor imaging evaluation and identify pivotal white matter changes after TAI that may affect axon vulnerability vs. recovery after brain injury.

  16. Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.

    Science.gov (United States)

    Relucio, Jenne; Menezes, Michael J; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Colognato, Holly

    2012-10-01

    The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2-/- mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2-/- VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2-/- corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.

  17. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

    Directory of Open Access Journals (Sweden)

    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years showed more improvement and no further disease progression than the later stages (11–15 years. However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

  18. The path from the choroid plexus to the subventricular zone: go with the flow!

    Directory of Open Access Journals (Sweden)

    Ana Mendanha Falcao

    2012-08-01

    Full Text Available In adult mammals, under physiological conditions, neurogenesis, the process of generating new functional neurons from precursor cells, occurs mainly in two brain areas: the subgranular zone in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ lining the walls of the brain lateral ventricles. Taking into account the location of the SVZ and the cytoarchitecture of this periventricular neural progenitor cell niche, namely the fact that the slow dividing primary progenitor cells (type B cells of the SVZ extend an apical primary cilium towards the brain ventricular space which is filled with cerebrospinal fluid (CSF, it becomes likely that the composition of the CSF can modulate both self-renewal, proliferation and differentiation of SVZ neural stem cells. The major site of CSF synthesis is the choroid plexus (CP; quite surprisingly, however, it is still largely unknown the contribution of molecules specifically secreted by the adult CP as modulators of the SVZ adult neurogenesis. This is even more relevant in light of recent evidence showing the ability of the CP to adapt its transcriptome and secretome to various physiologic and pathologic stimuli. By giving particular emphasizes to growth factors and axonal guidance molecules we will illustrate how CP-born molecules might play an important role in the SVZ niche cell population dynamics.

  19. Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.

    Directory of Open Access Journals (Sweden)

    Seong-Jin Yu

    Full Text Available Migration of new neuroprogenitor cells (NPCs from the subventricular zone (SVZ plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo. SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.

  20. Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.

    Science.gov (United States)

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.

  1. Changes in neural stem cells in the subventricular zone in a rat model of communicating hydrocephalus.

    Science.gov (United States)

    Li, Yan; Wu, Dongxue; Wu, Chunming; Qu, Zhenyun; Zhao, Yongshun; Li, Weihua; Wang, Jian; Li, Zhongmin

    2014-08-22

    Communicating hydrocephalus is a common type of hydrocephalus. At present, the prevalent treatment is to perform a ventriculo-peritoneal shunt, which, for reasons that are not clear, is sometimes ineffective. The subventricular zone (SVZ) of the lateral ventricles has been established as the primary site of adult neurogenesis. Following cerebral ischemia or brain injury, neural stem cells (NSCs) increase in the SVZ and can both differentiate into neurons and glial cells and respond to the injury. Neural stem cells, enabled by a complex repertoire of factors that precisely regulate the activation, proliferation, differentiation and integration of newborn cells, continuously generate new neurons. However, only a few systematic studies of the role of NSCs in hydrocephalus have been reported. In a rat model of communicating hydrocephalus, we recently showed that hydrocephalus caused the ventricular system to expand over time. We found that the number of NSCs in the SVZ peaked rapidly after hydrocephalus was established and decreased gradually over time until the cells disappeared. NSCs may be involved in the pathophysiology changes and repair process of hydrocephalus.

  2. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    Science.gov (United States)

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  3. SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex.

    Science.gov (United States)

    Brøchner, Christian B; Møllgård, Kjeld

    2016-01-01

    The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-labeling immunofluorescence. A few small rounded SSEA-4 and YKL-40 labeled cells were present in the radial glial BLBP positive proliferative zones adjacent to the lateral ganglionic eminence from 12th week post conception. With increasing age, a similarly stained cell population appeared more widespread in the subventricular zone. At midgestation, the entire subventricular zone showed patches of SSEA-4, YKL-40, and BLBP positive cells. Co-labeling with markers for radial glial cells (RGCs) and neuronal, glial, and microglial markers tested the lineage identity of this subpopulation of radial glial descendants. Adjacent to the ventricular zone, a minor fraction showed overlap with GFAP but not with nestin, Olig2, NG2, or S100. No co-localization was found with neuronal markers NeuN, calbindin, DCX or with markers for microglial cells (Iba-1, CD68). Moreover, the SSEA-4 and YKL-40 positive cell population in subventricular zone was largely devoid of Tbr2, a marker for intermediate neuronal progenitor cells descending from RGCs. YKL-40 has recently been found in astrocytes in the neuron-free fimbria, and both SSEA-4 and YKL-40 are present in malignant astroglial brain tumors. We suggest that the population of cells characterized by immunohistochemical combination of antibodies against SSEA-4 and YKL-40 and devoid of neuronal and microglial markers represent a yet unexplored astrogenic lineage illustrating the complexity of astroglial development.

  4. Local Administration of AAV-BDNF to Subventricular Zone Induces Functional Recovery in Stroke Rats

    OpenAIRE

    Seong-Jin Yu; Kuan-Yin Tseng; Hui Shen; Harvey, Brandon K.; Mikko Airavaara; Yun Wang

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-B...

  5. Dystroglycan Suppresses Notch to Regulate Stem Cell Niche Structure and Function in the Developing Postnatal Subventricular Zone.

    Science.gov (United States)

    McClenahan, Freyja K; Sharma, Himanshu; Shan, Xiwei; Eyermann, Christopher; Colognato, Holly

    2016-09-12

    While the extracellular matrix (ECM) is known to regulate neural stem cell quiescence in the adult subventricular zone (SVZ), the function of ECM in the developing SVZ remains unknown. Here, we report that the ECM receptor dystroglycan regulates a unique developmental restructuring of ECM in the early postnatal SVZ. Dystroglycan is furthermore required for ependymal cell differentiation and assembly of niche pinwheel structures, at least in part by suppressing Notch activation in radial glial cells, which leads to the increased expression of MCI, Myb, and FoxJ1, transcriptional regulators necessary for acquisition of the multiciliated phenotype. Dystroglycan also regulates perinatal radial glial cell proliferation and transition into intermediate gliogenic progenitors, such that either acute or constitutive loss of function in dystroglycan results in increased oligodendrogenesis. These findings reveal a role for dystroglycan in orchestrating both the assembly and function of the SVZ neural stem cell niche.

  6. Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

    Directory of Open Access Journals (Sweden)

    Jixian eWang

    2015-09-01

    Full Text Available Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 minutes transient middle cerebral artery occlusion (tMCAO. Then Tregs (1x105 were injected into the left lateral ventricle of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10 and transforming growth factor (TGF- signaling. We found that the number of BrdU+ cells in the subventricular zone was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here we conclude that activated Tregs enhanced neural stem cell proliferation in the subventricular zone of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated neural stem cell proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted neural stem cell proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke.

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

    Directory of Open Access Journals (Sweden)

    Rocío eTalaverón

    2015-10-01

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

  8. Mechanisms of oligodendrocyte regeneration from ventricular-subventricular zone-derived progenitor cells in white matter diseases

    Directory of Open Access Journals (Sweden)

    Takakuni eMaki

    2013-12-01

    Full Text Available White matter dysfunction is an important part of many CNS disorders including multiple sclerosis and vascular dementia. Within injured areas, myelin loss and oligodendrocyte death may trigger endogenous attempts at regeneration. However, during disease progression, remyelination failure may eventually occur due to impaired survival/proliferation, migration/recruitment, and differentiation of oligodendrocyte precursor cells (OPCs. The ventricular-subventricular zone (V-SVZ and the subgranular zone are the main sources of neural stem/progenitor cells (NSPCs, which can give rise to neurons as well as OPCs. Under normal conditions in the adult brain, the V-SVZ progenitors generate a large number of neurons with a small number of oligodendrocyte lineage cells. However, after demyelination, the fate of V-SVZ-derived progenitor cells shifts from neurons to OPCs, and these newly generated OPCs migrate to the demyelinating lesions to ease white matter damage. In this mini-review, we will summarize the recent studies on extrinsic (e.g., vasculature, extracellular matrix, cerebrospinal fluid and intrinsic (e.g., transcription factors, epigenetic modifiers factors, which mediate oligodendrocyte generation from the V-SVZ progenitor cells. A deeper understanding of the mechanisms that regulate the fate of V-SVZ progenitor cells may lead to new therapeutic approaches for ameliorating white matter dysfunction and damage in CNS disorders.

  9. BTG1 is required to maintain the pool of stem and progenitor cells of dentate gyrus and subventricular zone

    Directory of Open Access Journals (Sweden)

    Stefano eFarioli-Vecchioli

    2012-08-01

    Full Text Available Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ. Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons.Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at two months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit cell cycle after completing the S phase, highly express p53 and p21, and within 5 days undergo apoptosis. In SVZ we observed an equivalent decrease, associated to apoptosis, of Btg1-null stem cells, neuroblasts and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity.We conclude that the ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, likely reflecting the impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Thus, Btg1 appears to be required for maintaining adult stem and progenitor cells quiescence and self-renewal.

  10. 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.

  11. Cytoarchitecture of mouse and human subventricular zone in developing cerebral neocortex.

    Science.gov (United States)

    Tabata, Hidenori; Yoshinaga, Satoshi; Nakajima, Kazunori

    2012-01-01

    During cerebral neocortical development, excitatory neurons are generated from radial glial cells in the ventricular zone (VZ) or from secondary progenitor cells in the subventricular zone (SVZ); these neurons then migrate toward the pial surface. We have observed that post-mitotic neurons generated directly in the VZ accumulated just above the VZ with a multipolar morphology, while secondary progenitor cells having a long ascending process left the VZ faster than the post-mitotic neurons. Recent observations of human developing neocortex have revealed the existence of radial glia-like progenitors (oRG cells) in the SVZ. This type of progenitor was first thought to be human specific; however, similar cells have also been found in mouse neocortex, and the morphology of these cells resembled that of some of the secondary progenitor cells that we had previously observed, suggesting the existence of a common architecture for the developing neocortex among mammals. In this review, we discuss the nature of the SVZ and its similarities and differences between humans and mice.

  12. Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; Fekete, Saskia; Zhu, Anli; Frank, Melissa

    2010-09-01

    Neural stem/progenitor cell (NSP) biology and neurogenesis in adult central nervous system (CNS) are important both towards potential future therapeutic applications for CNS repair, and for the fundamental function of the CNS. In the present study, we report the characterization of NSP population from subventricular zone (SVZ) of neonatal piglet brain using in vivo and in vitro systems. We show that the nestin and vimentin-positive neural progenitor cells are present in the SVZ of the lateral ventricles of neonatal piglet brain. In vitro, piglet NSPs proliferated as neurospheres, expressed the typical protein of neural progenitors, nestin and a range of well-established neurodevelopmental markers. Upon dissociation and subculture, piglet NSPs differentiated into neurons and glial cells. Clonal analysis demonstrates that piglet NSPs are multipotent and retain the capacity to generate both glia and neurons. These cells expressed VEGF, VEGFR1, VEGFR2 and Neuropilin-1 and -2 mRNAs. Real time PCR revealed that SVZ NSPs from newborn piglet expressed total VEGF and all VEGF splice variants. These findings show that piglet NSPs may be helpful to more effectively design growth factor based strategies to enhance endogenous precursor cells for cell transplantation studies potentially leading to the application of this strategy in the nervous system disease and injury.

  13. Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice.

    Science.gov (United States)

    Song, Mingke; Yu, Shan Ping; Mohamad, Osama; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Jiang, Michael Qize; Wei, Ling

    2017-02-01

    Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain. In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release into SVZ region, evoked membrane currents, Ca(2+) influx and increased proliferation of SVZ neuroblasts, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum started 5days after stroke for 8days not only promoted cell proliferation but also the migration of SVZ neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ neuronal regulation via a semi-phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery. The benefits from stimulating endogenous glutamatergic activity suggest a novel regenerative strategy after ischemic stroke and other brain injuries.

  14. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia

    Indian Academy of Sciences (India)

    ROSANA S LOPES; MARCELO M CARDOSO; ARTHUR O SAMPAIO; MARIO SANTOS BARBOSA Jr; CELICE C SOUZA; MICHELLE C DA SILVA; ELANE MAGNO N FERREIRA; MARCO AURELIOM FREIRE; RAFAEL RODRIGUES LIMA; WALACE GOMES-LEAL

    2016-09-01

    Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die inthe ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored theeffects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation andneuroblast migration following experimental striatal stroke in adult rats. Animals were submitted toendothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline(i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronalloss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by countingNeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reducedmicroglia activation and the number of ED1^{+} cells in both 8 and 14 days post injury as compared withcontrols. There was an increase in the number of DCX^{+} cells in both SVZ and striatum at the same survivaltimes. Moreover, there was a decrease in the number of NeuN^{+} cells in indomethacin-treated animals ascompared with the control group at 8 days but not after 14 days post injury. Our results suggest thatindomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation inthe SVZ and migration to the ischaemic striatum following stroke.

  15. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

    Directory of Open Access Journals (Sweden)

    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  16. Traumatic brain injury reveals novel cell lineage relationships within the subventricular zone

    Directory of Open Access Journals (Sweden)

    Gretchen M. Thomsen

    2014-07-01

    Full Text Available The acute response of the rodent subventricular zone (SVZ to traumatic brain injury (TBI involves a physical expansion through increased cell proliferation. However, the cellular underpinnings of these changes are not well understood. Our analyses have revealed that there are two distinct transit-amplifying cell populations that respond in opposite ways to injury. Mash1+ transit-amplifying cells are the primary SVZ cell type that is stimulated to divide following TBI. In contrast, the EGFR+ population, which has been considered to be a functionally equivalent progenitor population to Mash1+ cells in the uninjured brain, becomes significantly less proliferative after injury. Although normally quiescent GFAP+ stem cells are stimulated to divide in SVZ ablation models, we found that the GFAP+ stem cells do not divide more after TBI. We found, instead, that TBI results in increased numbers of GFAP+/EGFR+ stem cells via non-proliferative means—potentially through the dedifferentiation of progenitor cells. EGFR+ progenitors from injured brains only were competent to revert to a stem cell state following brief exposure to growth factors. Thus, our results demonstrate previously unknown changes in lineage relationships that differ from conventional models and likely reflect an adaptive response of the SVZ to maintain endogenous brain repair after TBI.

  17. Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

    Energy Technology Data Exchange (ETDEWEB)

    Adeberg, Sebastian, E-mail: Sebastian.adeberg@med.uni-heidelberg [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); König, Laila; Bostel, Tilman; Harrabi, Semi; Welzel, Thomas [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany); DKFZ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg (Germany); Combs, Stephanie E. [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany)

    2014-11-15

    Purpose: We evaluated the influence of tumor location and tumor spread in primary glioblastoma (GBM), with respect to the subventricular zone (SVZ), on recurrence behavior, progression-free survival (PFS), and overall survival (OS). Methods and Materials: 607 patients (376 male and 231 female) with a median age of 61.3 years (range, 3.0-87.9 years) and primary GBM treated with radiation therapy (RT) from 2004 to 2012 at a single institution were included in this retrospective study. Preoperative images and follow-up examination results were assessed to evaluate tumor location. Tumors were classified according to the tumor location in relation to the SVZ. Results: The median PFS of the study population was 5.2 months (range, 1-91 months), and the median OS was 13.8 months (range, 1-102 months). Kaplan-Meier analysis showed that tumor location in close proximity to the SVZ was associated with a significant decline in PFS and OS (4.8 and 12.3 months, respectively; each P<.001). Furthermore, in cases where tumors were involved with the SVZ, distant cerebral progression (43.8%; P=.005) and multifocal progression (39.8%; P=.008) were more common. Interestingly, opening of the ventricle during the previous surgery showed no impact on PFS and OS. Conclusion: GBM in close proximity to the SVZ was associated with decreased survival and had a higher risk of multifocal or distant progression. Ventricle opening during surgery had no effect on survival rates.

  18. Enhancement of ventricular-subventricular zone-derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives.

    Science.gov (United States)

    Kaneko, Naoko; Kako, Eisuke; Sawamoto, Kazunobu

    2013-11-27

    In the postnatal mammalian brain, stem cells in the ventricular-subventricular zone (V-SVZ) continuously generate neuronal and glial cells throughout life. Genetic labeling of cells of specific lineages have demonstrated that the V-SVZ is an important source of the neuroblasts and/or oligodendrocyte progenitor cells (OPCs) that migrate toward injured brain areas in response to several types of insult, including ischemia and demyelinating diseases. However, this spontaneous regeneration is insufficient for complete structural and functional restoration of the injured brain, so interventions to enhance these processes are sought for clinical applications. Erythropoietin (EPO), a clinically applied erythropoietic factor, is reported to have cytoprotective effects in various kinds of insult in the central nervous system. Moreover, recent studies suggest that EPO promotes the V-SVZ-derived neurogenesis and oligodendrogenesis. EPO increases the proliferation of progenitors in the V-SVZ and/or the migration and differentiation of their progenies in and around injured areas, depending on the dosage, timing, and duration of treatment, as well as the type of animal model used. On the other hand, EPO has undesirable side effects, including thrombotic complications. We recently demonstrated that a 2-week treatment with the EPO derivative asialo-EPO promotes the differentiation of V-SVZ-derived OPCs into myelin-forming mature oligodendrocytes in the injured white matter of neonatal mice without causing erythropoiesis. Here we present an overview of the multifaceted effects of EPO and its derivatives in the V-SVZ and discuss the possible applications of these molecules in regenerative medicine.

  19. Enhancement of ventricular-subventricular zone-derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives

    Directory of Open Access Journals (Sweden)

    Naoko eKaneko

    2013-11-01

    Full Text Available In the postnatal mammalian brain, stem cells in the ventricular-subventricular zone (V-SVZ continuously generate neuronal and glial cells throughout life. Genetic labeling of cells of specific lineages have demonstrated that the V-SVZ is an important source of the neuroblasts and/or oligodendrocyte progenitor cells (OPCs that migrate toward injured brain areas in response to several types of insult, including ischemia and demyelinating diseases. However, this spontaneous regeneration is insufficient for complete structural and functional restoration of the injured brain, so interventions to enhance these processes are sought for clinical applications. Erythropoietin (EPO, a clinically applied erythropoietic factor, is reported to have cytoprotective effects in various kinds of insult in the central nervous system. Moreover, recent studies suggest that EPO promotes the V-SVZ-derived neurogenesis and oligodendrogenesis. EPO increases the proliferation of progenitors in the V-SVZ and/or the migration and differentiation of their progenies in and around injured areas, depending on the dosage, timing, and duration of treatment, as well as the type of animal model used. On the other hand, EPO has undesirable side effects, including thrombotic complications. We recently demonstrated that a two-week treatment with the EPO derivative asialo-EPO promotes the differentiation of V-SVZ-derived OPCs into myelin-forming mature oligodendrocytes in the injured white matter of neonatal mice without causing erythropoiesis. Here we present an overview of the multifaceted effects of EPO and its derivatives in the V-SVZ and discuss the possible applications of these molecules in regenerative medicine.

  20. Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke.

    Science.gov (United States)

    Heldmann, Ursula; Mine, Yutaka; Kokaia, Zaal; Ekdahl, Christine T; Lindvall, Olle

    2011-06-01

    Ischemic stroke induces migration of newly formed neuroblasts, generated by neural stem cells in the adult rat subventricular zone (SVZ), towards the injured striatum where they differentiate into mature neurons. Stroke also leads to accumulation of microglia in the SVZ but their role for neurogenesis is unclear. Here we developed a method for selective depletion of the macrophage antigen complex-1 (Mac-1)-expressing microglia population in the SVZ by intraventricular injection of the immunotoxin Mac-1-saporin in rats. We found that the vast majority of Mac-1+ cells were Iba-1+ microglia. The Mac-1+ population was heterogeneous and included both a small proliferative pool of cells, which was not affected by middle cerebral artery occlusion (MCAO), and a larger subpopulation that changed morphologically into a semi-activated state in response to the insult. This subpopulation did not increase its expression of the phagocytic marker ED1 but exhibited high levels of triggering receptor expressed on myeloid cells-2 (TREM-2), associated with alternative microglia activation. A minor portion of the SVZ Mac-1+ cells originated from the blood early after stroke, but this macrophage population became much more substantial at later stages. Almost 80% reduction of Mac-1-expressing microglia, caused by Mac-1 saporin delivered just before and at 1 week after MCAO, did not alter the numbers of newly formed neuroblasts in the striatum or their migratory distance. These findings indicate that the Mac-1-expressing microglia in the SVZ do not play a major role either for the number of neuroblasts which exit the SVZ or their migration in the striatum early following stroke.

  1. Activation of type 1 cannabinoid receptor (CB1R promotes neurogenesis in murine subventricular zone cell cultures.

    Directory of Open Access Journals (Sweden)

    Sara Xapelli

    Full Text Available The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive, neurons and astrocytes. Stimulation of the CB1R by (R-(+-Methanandamide (R-m-AEA increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation, at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca(2+]i in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

  2. Bone marrow stromal cells can promote the neurogenesis in subventricular zone in the rat with focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Pushuai Wen

    2010-01-01

    Full Text Available   Abstract Introdution: Stroke is one of the most common diseases caused by occlusion or rupture of blood vessels in brain. It brings heavily loads for families and societies. Although some new strategies including treatment of tissue plasminogen activator have been applied in the clinic, these methods do not have perfect effect. Accordingly, more effective therapeutic strategies need to be developed. This study was conducted to investigate the action of bone marrow stromal cells (BMSC on the neural stem cells in the subventricular zone of the rat after focal cerebral ischemia. Methods: The rats were induced to permanent focal cerebral ischemia models with middle cerebral artery occlusion (MCA0. Test groups consisted of three groups: MCAO alone, intravenous infusion of 1 ml PBS at 24 hours after MCAO, and intravenous infusion of 2×106 BMSCs 24 hours after MCAO. Then, the groups were divided to investigate at 7 and 14 days after MACO. Neurological functions were detected to use Zausinger evaluation; meanwhile, 5-bromodeoxyuridine was injected to label the proliferating cells in the subventricular zone, and double-immunofluoroscent technologies were used to identify the cell type.  Results: Neurological functional scores of BMSCs-treated group were higher than other two groups (p<0.05 at 7 and 14 days after MACO. BrdU-positive cells in SVZ of ipsilateral ischemia of BMSCs-treated group were more than two controls (p<0.05 at 14 days after MCAO; double-immunofluorescence label demonstrated that BrdU-positive cells co-located with markers of neuron and astrocyte.   Discussion: BMSCs can promote the neurological function of the rats with permanent focal cerebral ischemia, which may associate with the neurogenesis in the subventricular zone.

  3. Increased Subventricular Zone Radiation Dose Correlates With Survival in Glioblastoma Patients After Gross Total Resection

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Linda [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Duke University School of Medicine, Durham, North Carolina (United States); Guerrero-Cazares, Hugo [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Ye, Xiaobu [Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, Maryland (United States); Ford, Eric [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); McNutt, Todd; Kleinberg, Lawrence [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States); Lim, Michael; Chaichana, Kaisorn [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Quinones-Hinojosa, Alfredo, E-mail: aquinon2@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Redmond, Kristin, E-mail: kjanson3@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States)

    2013-07-15

    Purpose: Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients. Methods and Materials: The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years). Results: Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS

  4. Carbon nanotubes impregnated with subventricular zone neural progenitor cells promotes recovery from stroke

    Directory of Open Access Journals (Sweden)

    Moon SU

    2012-06-01

    Full Text Available Sung Ung Moon,1,* Jihee Kim,1,2,* Kiran Kumar Bokara,1,* Jong Youl Kim,1 Dongwoo Khang,3,4 Thomas J Webster,3,4 Jong Eun Lee1,21Department of Anatomy, 2Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; 3School of Engineering, 4Department of Orthopedics, Brown University, Providence, RI, USA*These authors contributed equally to this workAbstract: The present in vivo study was conducted to evaluate whether hydrophilic (HL or hydrophobic (HP carbon nanotubes (CNTs impregnated with subventricular zone neural progenitor cells (SVZ NPCs could repair damaged neural tissue following stroke. For this purpose, stroke damaged rats were transplanted with HL CNT-SVZ NPCs, HP CNT-SVZ NPCs, or SVZ NPCs alone for 1, 3, 5, and 8 weeks. Results showed that the HP CNT-SVZ NPC transplants improved rat behavior and reduced infarct cyst volume and infarct cyst area compared with the experimental control and the HL CNT-SVZ NPC and SVZ NPCs alone groups. The transplantation groups showed an increase in the expression of nestin (cell stemness marker and proliferation which was evident with the increased number of doublecortin and bromodeoxyuridine double-stained immunopositive cells around the lesion site. But, these effects were more prominent in the HP CNT-SVZ NPC group compared with the other transplantation groups. The HP CNT-SVZ NPC and HL CNT-SVZ NPC transplants increased the number of microtubule-associated protein 2 (marker for neurons and decreased the number of glial fibrillary acidic protein (marker for astroglial cells positive cells within the injury epicenter. The majority of the transplanted HP CNT-SVZ NPCs collectively broadened around the ischemic injured region and the SVZ NPCs differentiated into mature neurons, attained the synapse morphology (TUJ1, synaptophysin, and decreased microglial activation (CD11b/c [OX-42]. For these reasons, this study provided the first evidence that CNTs can improve

  5. Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries

    Institute of Scientific and Technical Information of China (English)

    Mariano Guardia Clausi; Ekta Kumari; Steven W.Levison

    2016-01-01

    There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone (SVZ). However, a comprehensive understanding of SVZ cell responses to brain in-juries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed lfow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how lfow cytometric analyses also have begun to reveal how speciifc cytokines, such as Leuke-mia inhibitory factor are coordinating SVZ responses to injury.

  6. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels.

    Science.gov (United States)

    Martínez-Martínez, Maria Ángeles; De Juan Romero, Camino; Fernández, Virginia; Cárdenas, Adrián; Götz, Magdalena; Borrell, Víctor

    2016-06-06

    The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease.

  7. Altered speeds and trajectories of neurons migrating in the ventricular and subventricular zones of the reeler neocortex.

    Science.gov (United States)

    Britto, Joanne M; Tait, Karen J; Johnston, Leigh A; Hammond, Vicki E; Kalloniatis, Michael; Tan, Seong-Seng

    2011-05-01

    The Reelin signaling pathway is essential for proper cortical development, but it is unclear to whether Reelin function is primarily important for cortical layering or neuron migration. It has been proposed that Reelin is perhaps required only for somal translocation but not glial-dependent locomotion. This implies that the location of neurons responding to Reelin is restricted to the outer regions of the cortical plate (CP). To determine whether Reelin is required for migration outside of the CP, we used time-lapse imaging to track the behavior of cells undergoing locomotion in the germinal zones. We focused on the migratory activity in the ventricular/subventricular zones where the first transition of bipolar to multipolar migration occurs and where functional Reelin receptors are known to be expressed. Despite Reelin loss, neurons had no difficulty in undergoing radial migration and indeed displayed greater migratory speed. Additionally, compared with the wild-type, reeler neurons displayed altered trajectories with greater deviation from a radial path. These results suggest that Reelin loss has early consequences for migration in the germinal zones that are portrayed as defective radial trajectories and migratory speeds. Together, these abnormalities can give rise to the increased cell dispersion observed in the reeler cortex.

  8. Functional electrical stimulation increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of rats with stroke

    Institute of Scientific and Technical Information of China (English)

    LIU Hui-hua; XIANG Yun; YAN Tie-bin; TAN Zhi-mei; LI Sheng-huo; HE Xiao-kuo

    2013-01-01

    Background Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis.In this study,we investigated whether postischemic FES could improve functional outcomes and modulate neurogenesis in the subventricular zone (SVZ) after focal cerebral ischemia.Methods Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion (MCAO) were randomly assigned to the control group,the placebo stimulation group,and the FES group.The rats in each group were further assigned to one of four therapeutic periods (1,3,7,or 14 days).FES was delivered 48 hours after the MCAO procedure and divided into two 10-minute sessions on each day of treatment with a 10-minute rest between them.Two intraperitoneal injections of bromodeoxyuridine (BrdU) were given 4 hours apart every day beginning 48 hours after the MCAO.Neurogenesis was evaluated by immunofluorescence staining.Wnt-3 which is strongly implicated in the proliferation and differentiation of neural stem cells (NSCs) was investigated by Western blotting analysis.The data wera subjected to oneway analysis of variance (ANOVA),followed by a Tukey/Kramer or Dunnett post hoc test.Results FES significantly increased the number of BrdU-positive cells and BrdU/glial flbrillary acidic protein doublepositive neural progenitor cells in the SVZ on days 7 and 14 of the treatment (P <0.05).The number of BrdU/doublecortin (DCX) double-positive migrating neuroblast cells in the ipsilateral SVZ on day 14 of the FES treatment group ((522.77±33.32) cells/mm2) was significantly increased compared with the control group ((262.58±35.11) cells/mm2,P <0.05) and the placebo group ((266.17±47.98) cells/mm2,P <0.05).However,only a few BrdU/neuron-specific nuclear protein-positive cells were observed by day 14 of the treatment.At day 7,Wnt-3 was upregulated in the ipsilateral SVZs of the rats receiving

  9. GABAA increases calcium in subventricular zone astrocyte-like cells through L- and T-type voltage-gated calcium channels

    Directory of Open Access Journals (Sweden)

    Stephanie Z Young

    2010-04-01

    Full Text Available In the adult neurogenic subventricular zone (SVZ, the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca2+ levels and tonic GABAA receptor activation. However, it is unknown whether, and if so how, GABAA receptor activity regulates intracellular Ca2+ dynamics in SVZ astrocytes. To monitor Ca2+ activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP promoter. GABAA receptor activation induced Ca2+ increases in 40-50% of SVZ astrocytes. GABAA-induced Ca2+ increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC. The L-type Ca2+ channel activator BayK 8644 increased the percentage of GABAA-responding astrocyte-like cells to 75%, suggesting that the majority of SVZ astrocytes express functional VGCCs. SVZ astrocytes also displayed spontaneous Ca2+ activity, the frequency of which was regulated by tonic GABAA receptor activation. These data support a role for ambient GABA in tonically regulating intracellular Ca2+ dynamics through GABAA receptors and VGCC in a subpopulation of astrocyte-like cells in the postnatal SVZ.

  10. Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

    Science.gov (United States)

    Wang, Jixian; Xie, Luokun; Yang, Chenqi; Ren, Changhong; Zhou, Kaijing; Wang, Brian; Zhang, Zhijun; Wang, Yongting; Jin, Kunlin; Yang, Guo-Yuan

    2015-01-01

    Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs (1 × 105) were injected into the left lateral ventricle (LV) of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-β) signaling. We found that the number of BrdU+ cells in the SVZ was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here, we conclude that activated Tregs enhanced neural stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted NSC proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke. PMID:26441532

  11. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage.

    Science.gov (United States)

    Feng, Zhichun; Liu, Jing; Ju, Rong

    2013-05-05

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  12. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Zhichun Feng; Jing Liu; Rong Ju

    2013-01-01

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2′-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2′- deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  13. Sequential activation of p75 and TrkB is involved in dendritic development of subventricular zone-derived neuronal progenitors in vitro.

    Science.gov (United States)

    Gascon, E; Vutskits, L; Zhang, H; Barral-Moran, M J; Kiss, P J; Mas, C; Kiss, J Z

    2005-01-01

    Dendritic arbor development of subventricular zone-derived interneurons is a critical step in their integration into functional circuits of the postnatal olfactory bulb. However, the mechanism and molecular control of this process remain unknown. In this study, we have developed a culture model where dendritic development of purified subventricular zone cells proceeds under serum-free conditions in the absence of added growth factors and non-neural cells. We demonstrate that the large majority of these cells in culture express GABA and elaborate dendritic arbors with spine-like protrusions but they do not possess axons. These neurons expressed receptors for neurotrophins including p75, TrkB and TrkC but not TrkA. Application of exogenous neurotrophins, including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and nerve growth factor (NGF), to cultures stimulated dendritic growth and led to more complex dendritic arbors during the initial 3 days in culture. Our results suggest that these effects are independent of Trk receptors and mediated by the p75/ceramide signaling pathway. We also show that brain-derived neurotrophic factor is the only neurotrophin that is able to influence late-phase dendritic development via TrkB receptor activation. These results suggest that dendritic arbor development of subventricular zone-derived cells may be regulated by neurotrophins through the activation of p75 and the TrkB receptor signaling pathways in a sequentially defined temporal pattern.

  14. Changes of evoked potential and expression of nestin in subventricular zones in rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    GAO Jie; WANG Yong-tang; WANG Li-li; ZENG Ling; WU Ya-min; SHAO Yang

    2007-01-01

    Objective:To study the characteristics of latency of somatosensory evoked potential (SEP)and motor evoked potential (MEP) and the expression of nestin in subventricular zones (SVZ) after persistent focal cerebral ischemia in rats. Methods: The model of cerebral ischemia in rats was made by middle cerebral artery occlusion (MCAO). All animals of ischemia were sacrificed after 12 h, 1 d, 3 d, 7 d,and 14 d to observe the changes of latency of SEP and MEP and to detect the expression of nestin, with an immunohistochemical approach. Results: The latencies of P1 (positive wave 1), N1 (negative wave 1) and P2 (positive wave 2) in SEP were significantly prolonged after MCAO. The latencies of N1 and N2 waves in MEP were postponed gradually and no statistical difference of latency of N1 wave was found in rats at 7d and 14 d after MCAO. The expression of nestin increased at 12 h, and showed a significant augmentation at 3 d and peaked at 7 d, then declined slightly at 14 d after MCAO. Conclusion: The cerebral ischemia prolonged the latency of EP waves and the expression of nestin was up-regulated and reached the peak at 7d, showing the ischemia induced the proliferation of nervous stem cells. The SEP and MEP may evaluate the proliferation in SVZ after brain ischemia.

  15. Ontogeny of CX3CR1-EGFP expressing cells unveil microglia as an integral component of the postnatal subventricular zone

    Directory of Open Access Journals (Sweden)

    Anna Lenice Ribeiro Xavier

    2015-02-01

    Full Text Available The full spectrum of cellular interactions within CNS neurogenic niches is still poorly understood. Only recently has the monocyte counterpart of the nervous system, the microglial cells, been described as an important cellular component in neurogenic niches. The present study sought to characterize the microglial population in the early postnatal subventricular zone (SVZ, the major site of postnatal neurogenesis, and in its anterior extension, the rostral migratory stream (RMS, a pathway for neuroblasts during their transit toward the olfactory bulb (OB layers. Analysis of the transgenic mice strain that has one of the locus of the constitutively expressed fractalkine CX3CR1 receptor replaced by the gene encoding the green fluorescent protein (EGFP circumvented the antigenic plasticity of the microglial cells. Here we show that common phenotypic markers of microglia do not reveal the full complement of these cells within the SVZ/RMS pathway. Remarkably, our analysis show that within the early SVZ/RMS pathway microglia are not proliferative and display a protracted development, retaining a more immature morphology than their counterparts outside germinal layers. Furthermore, during the first postnatal days microglia contact and phagocyte radial glia cells (RGs. Our results unveil microglial cells as a prominent component along the entire SVZ niche, together with neuroblasts and astroglial progenitors.

  16. Ontogeny of CX3CR1-EGFP expressing cells unveil microglia as an integral component of the postnatal subventricular zone.

    Science.gov (United States)

    Xavier, Anna L; Lima, Flavia R S; Nedergaard, Maiken; Menezes, João R L

    2015-01-01

    The full spectrum of cellular interactions within CNS neurogenic niches is still poorly understood. Only recently has the monocyte counterpart of the nervous system, the microglial cells, been described as an integral cellular component of neurogenic niches. The present study sought to characterize the microglia population in the early postnatal subventricular zone (SVZ), the major site of postnatal neurogenesis, as well as in its anterior extension, the rostral migratory stream (RMS), a pathway for neuroblasts during their transit toward the olfactory bulb (OB) layers. Here we show that microglia within the SVZ/RMS pathway are not revealed by phenotypic markers that characterize microglia in other regions. Analysis of the transgenic mice strain that has one locus of the constitutively expressed fractalkine CX3CR1 receptor replaced by the gene encoding the enhanced green fluorescent protein (EGFP) circumvented the antigenic plasticity of the microglia, thus allowing us to depict microglia within the SVZ/RMS pathway during early development. Notably, microglia within the early SVZ/RMS are not proliferative and display a protracted development, retaining a more immature morphology than their counterparts outside germinal layers. Furthermore, microglia contact and phagocyte radial glia cells (RG) processes, thereby playing a role on the astroglial transformation that putative stem cells within the SVZ niche undergo during the first postnatal days.

  17. Delivery of In Vivo Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures.

    Science.gov (United States)

    Ross, Heather H; Sandhu, Milap S; Sharififar, Sharareh; Fuller, David D

    2015-11-02

    Extended culture of neural stem/progenitor cells facilitates in vitro analyses to understand their biology while enabling expansion of cell populations to adequate numbers prior to transplantation. Identifying approaches to refine this process, to augment the production of all CNS cell types (i.e., neurons), and to possibly contribute to therapeutic cell therapy protocols is a high research priority. This report describes an easily applied in vivo "pre-conditioning" stimulus which can be delivered to awake, non-anesthetized animals. Thus, it is a non-invasive and non-stressful procedure. Specifically described are the procedures for exposing mouse or rat pups (aged postnatal day 1-8) to a brief (40-80 min) period of intermittent hypoxia (AIH). The procedures included in this video protocol include calibration of the whole-body plethysmography chamber in which pups are placed during AIH and the technical details of AIH exposure. The efficacy of this approach to elicit tissue-level changes in the awake animal is demonstrated through the enhancement of subsequent in vitro expansion and neuronal differentiation in cells harvested from the subventricular zone (SVZ). These results support the notion that tissue level changes across multiple systems could be observed following AIH, and support the continued optimization and establishment of AIH as a priming or conditioning modality for therapeutic cell populations.

  18. SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Møllgård, Kjeld

    2016-01-01

    The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-...... characterized by immunohistochemical combination of antibodies against SSEA-4 and YKL-40 and devoid of neuronal and microglial markers represent a yet unexplored astrogenic lineage illustrating the complexity of astroglial development. GLIA 2015....

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

    Science.gov (United States)

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

    2015-01-01

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

  20. S phase entry of neural progenitor cells correlates with increased blood flow in the young subventricular zone.

    Directory of Open Access Journals (Sweden)

    Benjamin Lacar

    Full Text Available The postnatal subventricular zone (SVZ contains proliferating neural progenitor cells in close proximity to blood vessels. Insults and drug treatments acutely stimulate cell proliferation in the SVZ, which was assessed by labeling cells entering S phase. Although G1-to-S progression is metabolically demanding on a minute-to-hour time scale, it remains unknown whether increased SVZ cell proliferation is accompanied by a local hemodynamic response. This neurovascular coupling provides energy substrates to active neuronal assemblies. Transcardial dye perfusion revealed the presence of capillaries throughout the SVZ that constrict upon applications of the thromboxane A(2 receptor agonist U-46119 in acute brain slice preparations. We then monitored in vivo blood flow using laser Doppler flowmetry via a microprobe located either in the SVZ or a mature network. U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and the striatum, which are near the ventricle. A 1-hour ventricular injection of epidermal and basic fibroblast growth factor (EGF and bFGF significantly increased the percentage of Sox2 transcription factor-positive cells in S phase 1.5 hours post-injection. This increase was accompanied by a sustained rise in blood flow in the SVZ but not in the striatum. Direct growth factor injections into the cortex did not alter local blood flow, ruling out direct effects on capillaries. These findings suggest that an acute increase in the number of G1-to-S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may provide energy and nutrient for cell cycle progression.

  1. ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice.

    Science.gov (United States)

    Wang, Jianping; Fu, Xiaojie; Zhang, Di; Yu, Lie; Li, Nan; Lu, Zhengfang; Gao, Yufeng; Wang, Menghan; Liu, Xi; Zhou, Chenguang; Han, Wei; Yan, Bo; Wang, Jian

    2017-01-01

    The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)(+) neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT(+) neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT(+) neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-α, IFN-γ, or TGF-β on day 7 after MCAO. We conclude that ChAT(+) neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Møllgård, Kjeld

    2016-01-01

    . Adjacent to the ventricular zone, a minor fraction showed overlap with GFAP but not with nestin, Olig2, NG2, or S100. No co-localization was found with neuronal markers NeuN, calbindin, DCX or with markers for microglial cells (Iba-1, CD68). Moreover, the SSEA-4 and YKL-40 positive cell population...... characterized by immunohistochemical combination of antibodies against SSEA-4 and YKL-40 and devoid of neuronal and microglial markers represent a yet unexplored astrogenic lineage illustrating the complexity of astroglial development. GLIA 2015....

  4. Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

    Energy Technology Data Exchange (ETDEWEB)

    Anna-Liisa Brownell

    2003-11-28

    Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons.

  5. Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    -treated mice subjected to cryo-lesion served as controls. The effects of gold-treatment were investigated by examining gold-induced growth factor expression (VEGF and FGF) in the first two weeks after the insult, and the extent of the neurostimulatory effect of gold was explored by comparing cell proliferation...... in the subventricular zone as judged by immunohistochemical staining for CDC47. Vimentin staining revealed a decrease in activated microglia and a transient astrogliosis in response to the gold liberation. Moreover, gold ions significantly increase the expression of VEGF and FGF following trauma and a significant...

  6. Optimizing culture medium composition to improve oligodendrocyte progenitor cell yields in vitro from subventricular zone-derived neural progenitor cell neurospheres.

    Science.gov (United States)

    Franco, Paula G; Pasquini, Juana M; Silvestroff, Lucas

    2015-01-01

    Neural Stem and Progenitor Cells (NSC/NPC) are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC) enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC.

  7. The subventricular zone in the immature piglet brain: anatomy and exodus of neuroblasts into white matter after traumatic brain injury.

    Science.gov (United States)

    Costine, Beth A; Missios, Symeon; Taylor, Sabrina R; McGuone, Declan; Smith, Colin M; Dodge, Carter P; Harris, Brent T; Duhaime, Ann-Christine

    2015-01-01

    Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled cortical impact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury

  8. The 5'-flanking region of the RP58 coding sequence shows prominent promoter activity in multipolar cells in the subventricular zone during corticogenesis.

    Science.gov (United States)

    Ohtaka-Maruyama, C; Hirai, S; Miwa, A; Takahashi, A; Okado, H

    2012-01-10

    Pyramidal neurons of the neocortex are produced from progenitor cells located in the neocortical ventricular zone (VZ) and subventricular zone (SVZ) during embryogenesis. RP58 is a transcriptional repressor that is strongly expressed in the developing brain and plays an essential role in corticogenesis. The expression of RP58 is strictly regulated in a time-dependent and spatially restricted manner. It is maximally expressed in E15-16 embryonic cerebral cortex, localized specifically to the cortical plate and SVZ of the neocortex, hippocampus, and parts of amygdala during brain development, and found in glutamatergic but not GABAergic neurons. Identification of the promoter activity underlying specific expression patterns provides important clues to their mechanisms of action. Here, we show that the RP58 gene promoter is activated prominently in multipolar migrating cells, the first in vivo analysis of RP58 promoter activity in the brain. The 5.3 kb 5'-flanking genomic DNA of the RP58 coding region demonstrates promoter activity in neurons both in vitro and in vivo. This promoter is highly responsive to the transcription factor neurogenin2 (Ngn2), which is a direct upstream activator of RP58 expression. Using in utero electroporation, we demonstrate that RP58 gene promoter activity is first detected in a subpopulation of pin-like VZ cells, then prominently activated in migrating multipolar cells in the multipolar cell accumulation zone (MAZ) located just above the VZ. In dissociated primary cultured cortical neurons, RP58 promoter activity mimics in vivo expression patterns from a molecular standpoint that RP58 is expressed in a fraction of Sox2-positive progenitor cells, Ngn2-positive neuronal committed cells, and Tuj1-positive young neurons, but not in Dlx2-positive GABAergic neurons. Finally, we show that Cre recombinase expression under the control of the RP58 gene promoter is a feasible tool for conditional gene switching in post-mitotic multipolar migrating

  9. Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2.

    Science.gov (United States)

    Arévalo-Martín, Angel; García-Ovejero, Daniel; Rubio-Araiz, Ana; Gómez, Oscar; Molina-Holgado, Francisco; Molina-Holgado, Eduardo

    2007-09-01

    The subventricular zone (SVZ) is a source of post-natal glial precursors that can migrate to the overlying white matter, where they may differentiate into oligodendrocytes. We showed that, in the post-natal SVZ ependymocytes, radial glia and astrocyte-like cells express cannabinoid receptor 1 (CB1), whereas cannabinoid receptor 2 (CB2) is found in cells expressing the polysialylated neural cell adhesion molecule. To study CB1 and CB2 function, post-natal rats were exposed to selective CB1 or CB2 agonists (arachidonyl-2-chloroethylamide and JWH-056, respectively) for 15 days. Accordingly, we found that CB1 activation increases the number of Olig2-positive cells in the dorsolateral SVZ, whereas CB2 activation increases polysialylated neural cell adhesion molecule expression in this region. As intense myelination occurs during the first weeks of post-natal development, we examined how modulating these factors affected the expression of myelin basic protein. Pharmacological administration of agonists and antagonists of CB1 and CB2 showed that the activation of both receptors is needed to augment the expression of myelin basic protein in the subcortical white matter.

  10. Early Inflammatory Responses Following Cell Grafting in the CNS Trigger Activation of the Subventricular Zone: A Proposed Model of Sequential Cellular Events.

    Science.gov (United States)

    Praet, Jelle; Santermans, Eva; Daans, Jasmijn; Le Blon, Debbie; Hoornaert, Chloé; Goossens, Herman; Hens, Niel; Van der Linden, Annemie; Berneman, Zwi; Ponsaerts, Peter

    2015-01-01

    While multiple rodent preclinical studies, and to a lesser extent human clinical trials, claim the feasibility, safety, and potential clinical benefit of cell grafting in the central nervous system (CNS), currently only little convincing knowledge exists regarding the actual fate of the grafted cells and their effect on the surrounding environment (or vice versa). Our preceding studies already indicated that only a minor fraction of the initially grafted cell population survives the grafting process, while the surviving cell population becomes invaded by highly activated microglia/macrophages and surrounded by reactive astrogliosis. In the current study, we further elaborate on early cellular and inflammatory events following syngeneic grafting of eGFP(+) mouse embryonic fibroblasts (mEFs) in the CNS of immunocompetent mice. Based on obtained quantitative histological data, we here propose a detailed mathematically derived working model that sequentially comprises hypoxia-induced apoptosis of grafted mEFs, neutrophil invasion, neoangiogenesis, microglia/macrophage recruitment, astrogliosis, and eventually survival of a limited number of grafted mEFs. Simultaneously, we observed that the cellular events following mEF grafting activates the subventricular zone neural stem and progenitor cell compartment. This proposed model therefore further contributes to our understanding of cell graft-induced cellular responses and will eventually allow for successful manipulation of this intervention.

  11. Abundant occurrence of basal radial glia in the subventricular zone of embryonic neocortex of a lissencephalic primate, the common marmoset Callithrix jacchus.

    Science.gov (United States)

    Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y; Kalinka, Alex T; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C; Okano, Hideyuki; Huttner, Wieland B; Borrell, Víctor

    2012-02-01

    Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type.

  12. Brain-derived neurotrophic factor levels influence the balance of migration and differentiation of subventricular zone cells, but not guidance to the olfactory bulb.

    Science.gov (United States)

    Petridis, Athanasios K; El Maarouf, Abderrahman

    2011-02-01

    New progenitor cells in the subventricular zone (SVZ) migrate rostrally and differentiate into interneurons in the olfactory bulb (OB) throughout life. Brain-derived neurotrophic factor (BDNF) may influence the normal progression of this migration. In the present study, mouse SVZ explant cultures were used to investigate how BDNF modulates the behavior of these migrating progenitors. Concentrations of BDNF in the physiological range (e.g. 1ng/mL) stimulated migration, whereas doses of 10 ng/mL or higher induced SVZ cell differentiation and reduced migration. Pharmacological inhibition of the mitogen-activated protein kinase (MAPK) pathway blocked the BDNF-induced differentiation of SVZ progenitors, indicating that differentiation of SVZ progenitors in response to high-dose BDNF is initiated through MAPK. Physiological concentrations of BDNF, like the presence of polysialic acid in the tissue, stimulated migration of cells from the explant without affecting the speed at which this occurs. Interestingly, in vivo immunohistochemical and molecular analysis showed similar levels of BDNF in both the SVZ and OB; that is, there was no positive gradient attracting SVZ cells towards the OB. Our data show that SVZ cells respond differently to different concentrations of BDNF.

  13. Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts.

    Directory of Open Access Journals (Sweden)

    Mahesh Kandasamy

    Full Text Available Huntington's disease (HD is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT. The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.

  14. Comparison of cortical and white matter traumatic brain injury models reveals differential effects in the subventricular zone and divergent Sonic hedgehog signaling pathways in neuroblasts and oligodendrocyte progenitors.

    Science.gov (United States)

    Mierzwa, Amanda J; Sullivan, Genevieve M; Beer, Laurel A; Ahn, Sohyun; Armstrong, Regina C

    2014-01-01

    The regenerative capacity of the central nervous system must be optimized to promote repair following traumatic brain injury (TBI) and may differ with the site and form of damage. Sonic hedgehog (Shh) maintains neural stem cells and promotes oligodendrogenesis. We examined whether Shh signaling contributes to neuroblast (doublecortin) or oligodendrocyte progenitor (neural/glial antigen 2 [NG2]) responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreER(T2);R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI. Injury to the cerebral cortex was produced with mild controlled cortical impact. Yellow fluorescent protein (YFP) cells decreased in cortical lesions. Total YFP cells increased in the subventricular zone (SVZ), indicating Shh pathway activation in SVZ cells, including doublecortin-labeled neuroblasts. The alternate TBI model produced traumatic axonal injury in the corpus callosum. YFP cells decreased within the SVZ and were rarely double labeled as NG2 progenitors. NG2 progenitors increased in the cortex, with a similar pattern in the corpus callosum. To further test the potential of NG2 progenitors to respond through Shh signaling, Smoothened agonist was microinjected into the corpus callosum to activate Shh signaling. YFP cells and NG2 progenitors increased in the SVZ but were not double labeled. This result indicates that either direct Smoothened activation in NG2 progenitors does not signal through Gli1 or that Smoothened agonist acts indirectly to increase NG2 progenitors. Therefore, in all conditions, neuroblasts exhibited differential Shh pathway utilization compared with oligodendrocyte progenitors. Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ.

  15. Comparison of Cortical and White Matter Traumatic Brain Injury Models Reveals Differential Effects in the Subventricular Zone and Divergent Sonic Hedgehog Signaling Pathways in Neuroblasts and Oligodendrocyte Progenitors

    Directory of Open Access Journals (Sweden)

    Amanda J. Mierzwa

    2014-09-01

    Full Text Available The regenerative capacity of the central nervous system must be optimized to promote repair following traumatic brain injury (TBI and may differ with the site and form of damage. Sonic hedgehog (Shh maintains neural stem cells and promotes oligodendrogenesis. We examined whether Shh signaling contributes to neuroblast (doublecortin or oligodendrocyte progenitor (neural/glial antigen 2 [NG2] responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreERT2;R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI. Injury to the cerebral cortex was produced with mild controlled cortical impact. Yellow fluorescent protein (YFP cells decreased in cortical lesions. Total YFP cells increased in the subventricular zone (SVZ, indicating Shh pathway activation in SVZ cells, including doublecortin-labeled neuroblasts. The alternate TBI model produced traumatic axonal injury in the corpus callosum. YFP cells decreased within the SVZ and were rarely double labeled as NG2 progenitors. NG2 progenitors increased in the cortex, with a similar pattern in the corpus callosum. To further test the potential of NG2 progenitors to respond through Shh signaling, Smoothened agonist was microinjected into the corpus callosum to activate Shh signaling. YFP cells and NG2 progenitors increased in the SVZ but were not double labeled. This result indicates that either direct Smoothened activation in NG2 progenitors does not signal through Gli1 or that Smoothened agonist acts indirectly to increase NG2 progenitors. Therefore, in all conditions, neuroblasts exhibited differential Shh pathway utilization compared with oligodendrocyte progenitors. Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ.

  16. A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

    DEFF Research Database (Denmark)

    Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.

    2015-01-01

    found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low...... STATEMENT: Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural...

  17. Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

    Directory of Open Access Journals (Sweden)

    Eric eLewitus

    2013-08-01

    Full Text Available There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly and presence (gyrencephaly of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- versus connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons towards the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.

  18. Mosaic Subventricular Origins of Forebrain Oligodendrogenesis

    Science.gov (United States)

    Azim, Kasum; Berninger, Benedikt; Raineteau, Olivier

    2016-01-01

    In the perinatal as well as the adult CNS, the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates neurons and oligodendrocytes (OLs), the myelin forming cells of the CNS. Recent advances in the field are beginning to shed light regarding SVZ heterogeneity, with the existence of spatially segregated microdomains that are intrinsically biased to generate phenotypically distinct neuronal populations. Although most research has focused on this regionalization in the context of neurogenesis, newer findings underline that this also applies for the genesis of OLs under the control of specific patterning molecules. In this mini review, we discuss the origins as well as the mechanisms that induce and maintain SVZ regionalization. These come in the flavor of specific signaling ligands and subsequent initiation of transcriptional networks that provide a basis for subdividing the SVZ into distinct lineage-specific microdomains. We further emphasize canonical Wnts and FGF2 as essential signaling pathways for the regional genesis of OL progenitors from NSCs of the dorsal SVZ. This aspect of NSC biology, which has so far received little attention, may unveil new avenues for appropriately recruiting NSCs in demyelinating diseases. PMID:27047329

  19. Mosaic subventricular origins of forebrain oligodendroglia

    Directory of Open Access Journals (Sweden)

    Kasum eAzim

    2016-03-01

    Full Text Available In the perinatal as well as the adult CNS, the subventricular zone (SVZ of the forebrain is the largest and most active source of neural stem cells (NSCs that generates neurons and oligodendrocytes (OLs, the myelin forming cells of the CNS. Recent advances in the field are beginning to shed light regarding SVZ heterogeneity, with the existence of spatially segregated microdomains that are intrinsically biased to generate phenotypically distinct neuronal populations. Although most research has focused on this regionalization in the context of neurogenesis, newer findings underline that this also applies for the genesis of OLs under the control of specific patterning molecules. In this mini review, we discuss the origins as well as the mechanisms that induce and maintain SVZ regionalization. These come in the flavor of specific signaling ligands and subsequent initiation of transcriptional networks that provide a basis for subdividing the SVZ into distinct lineage-specific microdomains. We further emphasize canonical Wnt and FGF2 as essential signaling pathways for the regional genesis of OL progenitors from NSCs of the dorsal SVZ. This aspect of NSC biology, which has so far received little attention, may unveil new avenues for appropriately recruiting NSCs in demyelinating diseases.

  20. Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

    Directory of Open Access Journals (Sweden)

    Valentina eOlivera-Pasilio

    2014-09-01

    Full Text Available Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24hs and long (30d chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers, sparse slow cycling (potentially stem cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones.

  1. Neurogenesis in the adult olfactory bulb

    Institute of Scientific and Technical Information of China (English)

    Angela Pignatelli; Cristina Gambardella; Ottorino Belluzzi

    2011-01-01

    Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles. Cells of the subventricular zone divide and migrate via the rostral migratory stream to the olfactory bulb where they differentiate into granule and periglomerular cells. With the discovery of large-scale neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Although many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. In this review we highlight the main studies investigating factors that regulate neurogenesis in the subventricular zone, neuronal migration to the olfactory bulb, neuronal integration into the existing bulbar network and shortly discuss the functional meaning of this process.

  2. Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival

    Science.gov (United States)

    d’Anglemont de Tassigny, Xavier; Sirerol-Piquer, M Salomé; Gómez-Pinedo, Ulises; Pardal, Ricardo; Bonilla, Sonia; Capilla-Gonzalez, Vivian; López-López, Ivette; De la Torre-Laviana, Francisco Javier; García-Verdugo, José Manuel; López-Barneo, José

    2015-01-01

    Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia. PMID:27774479

  3. The neural elements in the lining of the ventricular-subventricular zone: making an old story new by high-resolution scanning electron microscopy.

    Science.gov (United States)

    Haemmerle, Carlos Alexandre Dos Santos; Nogueira, Maria Inês; Watanabe, Ii-Sei

    2015-01-01

    The classical description of the neural elements that compose the lining of brain ventricles introduces us to the single layer of ependymal cells. However, new findings, especially in the lateral ventricle (LV)-the major niche for the generation of new neurons in the adult brain-have provided information about additional cell elements that influence the organization of this part of the ventricular system and produce important contributions to neurogenesis. To complement the cell neurochemistry findings, we present a three-dimensional in situ description that demonstrates the anatomical details of the different types of ciliated cells and the innervation of these elements. After processing adult rat brains for ultrastructural analysis by high-resolution scanning electron microscopy (HRSEM) and transmission electron microscopy, we observed a heterogeneous pattern of cilia distribution at the different poles of the LV surface. Furthermore, we describe the particular three-dimensional aspects of the ciliated cells of the LV, in addition the fiber bundles and varicose axons surrounding these cells. Therefore, we provide a unique ultrastructural description of the three-dimensional in situ organization of the LV surface, highlighting its innervation, to corroborate the available neurochemical and functional findings regarding the factors that regulate this neurogenic niche.

  4. The neural elements in the lining of the ventricular-subventricular zone: making an old story new by high-resolution scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Dos Santos Haemmerle

    2015-10-01

    Full Text Available The classical description of the neural elements that compose the lining of brain ventricles introduces us to the single layer of ependymal cells. However, new findings, especially in the lateral ventricle - the major niche for the generation of new neurons in the adult brain - have provided information about additional cell elements that influence the organization of this part of the ventricular system and produce important contributions to neurogenesis. To complement the cell neurochemistry findings, we present a three-dimensional in situ description that demonstrates the anatomical details of the different types of ciliated cells and the innervation of these elements. After processing adult rat brains for ultrastructural analysis by high-resolution scanning electron microscopy and transmission electron microscopy, we observed a heterogeneous pattern of cilia distribution at the different poles of the lateral ventricle surface. Furthermore, we describe the particular three-dimensional aspects of the ciliated cells of the lateral ventricle, in addition the fiber bundles and varicose axons surrounding these cells. Therefore, we provide a unique ultrastructural description of the three-dimensional in situ organization of the lateral ventricle surface, highlighting its innervation, to corroborate the available neurochemical and functional findings regarding the factors that regulate this neurogenic niche.

  5. Genetically targeting new neurons in the adult hippocampus

    Institute of Scientific and Technical Information of China (English)

    Zhengang Yang; Guo-Li Ming; Hongjun Song

    2011-01-01

    @@ Neurogenesis, the birth of new neu-rons from neural stem cells, is known to occur throughout life in two specific regions of the adult mammalian brain, the subgranular zone/hippocampal dentate gyms and the subventricular zone/olfactory bulb [1-3]. Adult neuro-genesis is a multi-step process (Figure 1), which includes proliferation and fate specification of adult neural stem cells, morphogenesis, migration, axonal and dendritic development, survival, and synaptic integration by newborn neurons [4].

  6. New neurons in the adult brain : The role of sleep and consequences of sleep loss

    NARCIS (Netherlands)

    Meerlo, Peter; Mistiberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis; Mistlberger, Ralph E.

    2009-01-01

    Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a ma

  7. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  8. Histone deacetylase inhibitors SAHA and sodium butyrate block G1-to-S cell cycle progression in neurosphere formation by adult subventricular cells

    Directory of Open Access Journals (Sweden)

    Doughty Martin L

    2011-05-01

    Full Text Available Abstract Background Histone deacetylases (HDACs are enzymes that modulate gene expression and cellular processes by deacetylating histones and non-histone proteins. While small molecule inhibitors of HDAC activity (HDACi are used clinically in the treatment of cancer, pre-clinical treatment models suggest they also exert neuroprotective effects and stimulate neurogenesis in neuropathological conditions. However, the direct effects of HDACi on cell cycle progression and proliferation, two properties required for continued neurogenesis, have not been fully characterized in adult neural stem cells (NSCs. In this study, we examined the effects of two broad class I and class II HDACi on adult mouse NSCs, the hydroxamate-based HDACi suberoylanilide hydroxamic acid (vorinostat, SAHA and the short chain fatty acid HDACi sodium butyrate. Results We show that both HDACi suppress the formation of neurospheres by adult mouse NSCs grown in proliferation culture conditions in vitro. DNA synthesis is significantly inhibited in adult mouse NSCs exposed to either SAHA or sodium butyrate and inhibition is associated with an arrest in the G1 phase of the cell cycle. HDACi exposure also resulted in transcriptional changes in adult mouse NSCs. Cdk inhibitor genes p21 and p27 transcript levels are increased and associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27. mRNA levels for notch effector Hes genes and Spry-box stem cell transcription factors are downregulated, whereas pro-neural transcription factors Neurog1 and Neurod1 are upregulated. Lastly, we show HDAC inhibition under proliferation culture conditions leads to long-term changes in cell fate in adult mouse NSCs induced to differentiate in vitro. Conclusion SAHA and sodium butyrate directly regulate cdk inhibitor transcription to control cell cycle progression in adult mouse NSCs. HDAC inhibition results in G1 arrest in adult mouse NSCs and transcriptional changes

  9. 缺氧缺血对人类胚胎脑室管膜下区神经细胞亚群的影响%Effects of hypoxia-ischemia on different neural cells in subventricular zone of human fetus

    Institute of Scientific and Technical Information of China (English)

    张燕舞; 陈燕惠

    2008-01-01

    higher survival rate than neurons and oligodendrocyte progenitors.%目的 研究缺氧缺血对妊娠中期人类胚胎脑室管膜下区(subventricular zone,SVZ)神经细胞亚群的影响.方法 取即刻解离的妊娠中期人类胚胎脑SVZ细胞,分缺氧缺血组(HI组)和对照组短时培养.以氧糖缺失法(OGD)制备缺氧缺血损伤细胞模型.培养前以细胞成活率评价损伤程度,培养后以细胞特异性标志蛋白nestin、MAP2、GFAP、PDGFRa及RCA120的抗体通过免疫荧光细胞化学法分别鉴定神经干细胞(NSCs)、神经元、星形胶质细胞、少突胶质祖细胞及小胶质细胞,比较其百分含量.结果 HI组的细胞成活率(63.41%±0.06%),明显低于正常组(98.9%±0.01%)(P<0.001),短时培养后HI组中细胞亚群中含量最高的是GFAP(+)的星形胶质细胞56.48%±0.03%,其次为神经干细胞NSCs 22.47%±0.03%而PDGFRa(+)的少突胶质祖细胞含量最低;在对照组中最高则为MAP2(+)的神经元48.81%±0.03%,其次为GFAP(+)的星形胶质细胞32.31%±0.03%.含量最少的为小胶质细胞1.15%±0.01%.结论 妊娠中期人类胚胎脑SVZ含有NSCs、神经元、星形胶质细胞、少突胶质祖细胞和小胶质细胞,缺氧缺血对SVZ神经细胞损伤明显,不同细胞对缺氧缺血损伤的耐受性不同:NSCs、星形胶质细胞对缺氧缺血损伤的耐受性相对强于神经元、少突胶质祖细胞.

  10. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Directory of Open Access Journals (Sweden)

    Patricia eRivera

    2015-09-01

    Full Text Available Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10% or sucrose liquid diets for two weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+ and the replicating cell DNA marker 5-bromo-2’-deoxyuridine (BrdU+ in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ, subventricular zone of lateral ventricles (SVZ and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3±1.1 g/kg/day after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ and hypothalamus. The treatments (URB597, ACEA, JWH133 exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  11. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Science.gov (United States)

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  12. 局灶缺血性脑卒中大鼠侧脑室下带Shh信号通路成分的动态表达%Dynamic Changes of the Expression of Sonic Hedgehog Signaling Pathway in the Subventricular Zone After Focal Cerebral Ischemia in Rats

    Institute of Scientific and Technical Information of China (English)

    范层层; 杨琴; 陈娜; 吴兆敏; 黄家贵

    2011-01-01

    通过研究Sonic hedgehog (Shh)信号通路成分在局灶缺血性脑卒中大鼠侧脑室下带(subventricular zone,SVZ)的动态表达,初步探讨该通路在局灶性缺血性脑卒中后神经再生的调控作用.将84只健康成年雄性SD大鼠随机分为正常组(n=12)、假手术组(n=12)、缺血6、12、24 h和3、7d,共7组(n=12).采用线栓法制备大鼠右侧大脑中动脉阻断(middle cerebral artery occlussion,MCAO)模型.分别应用逆转录聚合酶链反应(RT-PCR)、免疫组化、免疫印迹法检测局灶脑缺血大鼠侧脑室下带Shh、Gli1 mRNA和蛋白变化.与正常组比较,Shh、Gli1mRNA和蛋白在假手术组表达变化不明显(P>0.05),模型组6h表达增高(P<0.01),24 h达峰值(P<0.01),3d时接近正常水平(P>0.05),7d表达又升高(P<0.01).缺血性脑卒中可以上调Shh信号通路成分在SVZ区的表达,提示Shh信号通路可能参与卒中后神经再生机制的调控.%To study the expression changes of Shh signaling pathway in the subventricular zone (SVZ) at different times after focal cerebral ischemia and find out whether the Shh pathway is involved in the regulation of the differentiation of the proliferated neural precursor cells in the SVZ under ischemic conditions. Eighty-four SD rats were divided into normal control group, sham operation group, experimental group at 6, 12, 24 h and 3, 7 d (n=l2 for time point) after surgery. Experimental group was made by filament occlusion of right middle cerebral artery. RT-PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein levels of Shh and Glil in the SVZ. Compared with the normal control group, the protein and mRNA expressions of Shh and Glil were not significantly changed in the sham operation (P>0.05). The protein and mRNA expressions of Shh and Glil were increased significantly at 6 h (P0.05) and increased significantly at 7 days (P<0.01) in experimental group. The up-regulation of the protein and mRNA levels

  13. Cellular organization of the central canal ependymal zone, a niche of latent neural stem cells in the adult mammalian spinal cord.

    Science.gov (United States)

    Hamilton, L K; Truong, M K V; Bednarczyk, M R; Aumont, A; Fernandes, K J L

    2009-12-15

    A stem cell's microenvironment, or "niche," is a critical regulator of its behaviour. In the adult mammalian spinal cord, central canal ependymal cells possess latent neural stem cell properties, but the ependymal cell niche has not yet been described. Here, we identify important similarities and differences between the central canal ependymal zone and the forebrain subventricular zone (SVZ), a well-characterized niche of neural stem cells. First, direct immunohistochemical comparison of the spinal cord ependymal zone and the forebrain SVZ revealed distinct patterns of neural precursor marker expression. In particular, ependymal cells in the spinal cord were found to be bordered by a previously uncharacterized sub-ependymal layer, which is relatively less elaborate than that of the SVZ and comprised of small numbers of astrocytes, oligodendrocyte progenitors and neurons. Cell proliferation surrounding the central canal occurs in close association with blood vessels, but unlike in the SVZ, involves mainly ependymal rather than sub-ependymal cells. These proliferating ependymal cells typically self-renew rather than produce transit-amplifying progenitors, as they generate doublets of progeny that remain within the ependymal layer and show no evidence of a lineage relationship to sub-ependymal cells. Interestingly, the dorsal pole of the central canal was found to possess a sub-population of tanycyte-like cells that express markers of both ependymal cells and neural precursors, and their presence correlates with higher numbers of dorsally proliferating ependymal cells. Together, these data identify key features of the spinal cord ependymal cell niche, and suggest that dorsal ependymal cells possess the potential for stem cell activity. This work provides a foundation for future studies aimed at understanding ependymal cell regulation under normal and pathological conditions.

  14. Vascular regulation of adult neurogenesis under physiological and pathological conditions

    Directory of Open Access Journals (Sweden)

    Masato eSawada

    2014-03-01

    Full Text Available Neural stem cells in the mammalian adult brain continuously produce new neurons throughout life. Accumulating evidence in rodents suggests that various aspects of adult neurogenesis, including the genesis, migration, and maturation of new neurons, are regulated by factors derived from blood vessels and their microenvironment. Brain injury enhances both neurogenesis and angiogenesis, thereby promoting the cooperative regeneration of neurons and blood vessels. In this paper, we briefly review the mechanisms for the vascular regulation of adult neurogenesis in the ventricular-subventricular zone under physiological and pathological conditions, and discuss their clinical potential for brain regeneration strategies.

  15. Impaired adult olfactory bulb neurogenesis in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Kohl Zacharias

    2010-09-01

    Full Text Available Abstract Background Huntington's disease (HD is an autosomal dominant neurodegenerative disorder linked to expanded CAG-triplet nucleotide repeats within the huntingtin gene. Intracellular huntingtin aggregates are present in neurons of distinct brain areas, among them regions of adult neurogenesis including the hippocampus and the subventricular zone/olfactory bulb system. Previously, reduced hippocampal neurogenesis has been detected in transgenic rodent models of HD. Therefore, we hypothesized that mutant huntingtin also affects newly generated neurons derived from the subventricular zone of adult R6/2 HD mice. Results We observed a redirection of immature neuroblasts towards the striatum, however failed to detect new mature neurons. We further analyzed adult neurogenesis in the granular cell layer and the glomerular layer of the olfactory bulb, the physiological target region of subventricular zone-derived neuroblasts. Using bromodeoxyuridine to label proliferating cells, we observed in both neurogenic regions of the olfactory bulb a reduction in newly generated neurons. Conclusion These findings suggest that the striatal environment, severely affected in R6/2 mice, is capable of attracting neuroblasts, however this region fails to provide sufficient signals for neuronal maturation. Moreover, in transgenic R6/2 animals, the hostile huntingtin-associated microenvironment in the olfactory bulb interferes with the survival and integration of new mature neurons. Taken together, endogenous cell repair strategies in HD may require additional factors for the differentiation and survival of newly generated neurons both in neurogenic and non-neurogenic regions.

  16. 表皮生长因子和碱性成纤维细胞生长因子对人胎脑室下区神经干细胞增殖分化的影响%Effect of epidermal growth factor and basic fibroblast growth factor on neural stem cells isolated from subventricular zone of human embryonic brain

    Institute of Scientific and Technical Information of China (English)

    尹晓娟; 封志纯

    2006-01-01

    differentiation of neural stem cells (NSCs) cause great difficulties for clinical application.Therefore, it is the key to solving the problem to investigate the proliferation and differentiation condition of NSCs.OBJECTIVE: To observe the effects of epidermal growth factor (EGF)and basic fibroblast growth factor (bFGF) on the proliferation and differentiation of neural stem cells of human embryonic brain.DESIGN: A randomised and controlled experiment taking cultured human embryonic stem cells as subjects.SETTING: Department of Pediatrics of Zhujiang Hospital, the First Military Medical University of Chinese PLA.MATERIALS: This experiment was conducted at the Central Laboratory of the Department of Pediatrics of Chinese PLA from January to May 2004.Two 16-week embryos from induced labor by water bags voluntarily were chosen at random from the Department of Obstetrics in a tertiary hospital in Guangzhou (Informed consent was obtained from the parents of the fetuses). Then, cells in the subventricular zone were cultured in serum-free medium and serum medium, respectively.METHODS: Primary cells of subventricular zone of human embryonic brain were cultured with serum-free nedium containing EGF, bFGF and EGF + bFGF. The concentration of two growth factors was both 20 μg/L;experiment of differentiation was performed on the cell neurospheres cultured from the primary generation with serum culture medium; differentia tive cells were detected with immonohistochemical technique.MAIN OUTCOME MEASURES: The number of neurospheres and the change of neurons and gliocytes from neurospheres in each group.RESULTS: ① There was no significant difference in the number of primary neurospheres between bFGF group and EGF+bFGF group [(150.3±14.9) /well vs (173.6±26.4)/we11, P > 0.05] , but the number in the two groups was both more than that in EGF group [(99.5±14.9)/we11, P < 0.01].② The neurons differentiated from neurospheres in bFGF group and EGF+bFGF group outnumbered those in EGF group

  17. 联合地塞米松治疗与肺炎链球菌脑膜炎室管膜下区碱性成纤维细胞生长因子表达的关系%The relationship between dexamethasone and the expression of basic fibroblast growth factor in subventricular zone of experimental streptococcus pneumoniae meningitis

    Institute of Scientific and Technical Information of China (English)

    赵秀英; 李玲; 廖锋; 向伟

    2013-01-01

    Objective To investigate the relationship between dexamethasone (DEX) and the expression of basic fibroblast growth factor (bFGF) in subventricular zone (SVZ) of experimental streptococcus pneumoniae meningitis. Methods Forty 3-week-old rats were used to develop the model of streptococcus pneumoniae meningitis, and were randomly divided into 4 groups of 10 rats each, antibiotic group, antibiotic plus DEX group, infection control group and normal control group. The expression level of bFGF in SVZ was detected by immunohistochemical staining. Results The expression level of bFGF in SVZ of rats in antibiotic group was similar to that of rats in infection control group (P>O.05). However, the expression level of bFGF in SVZ of rats in antibiotic plus DEX group was significantly higher than that of rats in antibiotic group and infection control group (P<0.01). Conclusions In the course of streptococcus pneumoniae meningitis, the combination therapy of antibiotics and DEX can up-regulate the expression level of bFGF in SVZ, which may promote neurogenesis and protect against brain injury in bacterial meningitis.%目的 探讨联合地塞米松(DEX)治疗与肺炎链球菌脑膜炎脑生发区域-室管膜下区(SVZ)碱性成纤维细胞生长因子(bFGF)表达的关系.方法 40只3周龄大鼠建立肺炎链球菌脑膜炎模型,分为抗生素组、抗生素联合DEX组、感染对照组、正常对照组,每组10只.免疫组化检测脑组织bFGF的表达.结果 抗生素组大鼠SVZ中的bFGF表达与感染对照组差异无统计学意义(P>0.05),而使用抗生素联合DEX组大鼠bFGF表达高于抗生素治疗组及感染对照组,差异均有统计学意义(P<0.01).结论 在肺炎链球菌脑膜炎病程中,联合DEX治疗可以上调bFGF在SVZ中的表达,可能有利于其促进神经生发,有利于抵御细菌性脑膜炎脑损伤.

  18. Artesunate promotes proliferation of rat neural stem cells from subventricular zone via PI3K-Akt pathway in vitro%青蒿琥酯通过PI3K-Akt通路促进大鼠室管膜下区神经干细胞增殖的体外研究

    Institute of Scientific and Technical Information of China (English)

    葛红飞; 左世伦; 李强; 谭亮; 吴江怡; 蒋周阳; 喻安永; 兰川; 胡荣

    2015-01-01

    目的 探讨青蒿琥酯(artesunate,ART)对室管膜下区(subventricular zone,SVZ)神经干细胞(neural stem cells,NSCs)增殖的影响.方法 不同浓度的ART(400 nmol/L、800 nmol/L、1.6 μmol/L、3.2 μmol/L)作用于NSCs 24 h后,采用CCK-8法检测其对NSCs增殖的影响.促增殖作用明显的800 nmol/L ART组加入10 μmol/L PI3K-Akt通路阻断剂(LY294002),采用CCK-8法检测该通路对NSCs增殖的影响;分别设置空白对照组、LY294002组、800 nmol/L ART组、800 nmol/L ART+ LY294002组,待细胞培养24h时,行Ki-67免疫荧光染色观察ART对NSCs增殖的影响及PI3K-Akt通路在其中的作用,同时采用Western blot检测各组Nestin、Akt及p-Akt蛋白的表达水平.结果 ①CCK-8法检测结果显示800 nmol/L ART组在波长450 nm处的光密度值较空白对照组明显升高,在加入LY294002后,其光密度值明显下降(P<0.05),与空白对照组水平相当;②Ki-67免疫荧光染色结果提示800 nmol/L ART可促进NSCs增殖,LY294002可抑制这一作用;③Western blot检测结果显示:神经干细胞表面标志蛋白Nestin及p-Akt蛋白表达水平在800 nmol/L ART组明显上调,在加入LY294002后两者表达水平均下调(P<0.05).结论 ART可在体外促进SVZ区NSCs的增殖,其机制与PI3K-Akt信号通路相关.

  19. Migrating neuroblasts in the adult human brain: a stream reduced to a trickle

    Institute of Scientific and Technical Information of China (English)

    Miriam E van Strien; Simone A van den Berge; Elly M Hol

    2011-01-01

    It has long been thought that neurogenesis (birth of neurons) in the mammalian brain only occurs while the central nervous system is still developing.Although the first indications to the contrary already appeared in the 1960s,it took more than 30 years for the neuroscience community to accept that the mammalian adult brain also generates new neurons.Today it is completely accepted that neurogenesis occurs in two mammalian adult brain areas,the subventricular zone (SVZ) near the lateral ventricles and the subgranular zone in the hippocampus.

  20. Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld

    Science.gov (United States)

    Ferholt, Beth; Lecusay, Robert

    2010-01-01

    This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…

  1. Adult neural stem cells stake their ground.

    Science.gov (United States)

    Lim, Daniel A; Alvarez-Buylla, Arturo

    2014-10-01

    The birth of new neurons in the walls of the adult brain lateral ventricles has captured the attention of many neuroscientists for over 2 decades, yielding key insights into the identity and regulation of neural stem cells (NSCs). In the adult ventricular-subventricular zone (V-SVZ), NSCs are a specialized form of astrocyte that generates several types of neurons for the olfactory bulb. In this review, we discuss recent findings regarding the unique organization of the V-SVZ NSC niche, the multiple regulatory controls of neuronal production, the distinct regional identities of adult NSCs, and the epigenetic mechanisms that maintain adult neurogenesis. Understanding how V-SVZ NSCs establish and maintain lifelong neurogenesis continues to provide surprising insights into the cellular and molecular regulation of neural development.

  2. 蛋白酶体抑制剂MG132对脑室室管膜下区神经干细胞增殖潜能的影响%Effects of proteasome inhibitor MG132 on proliferation of neural stem cells in subventricular zone

    Institute of Scientific and Technical Information of China (English)

    赵云鹤; 张卫国; 朱茜; 杨桂姣; 陆利

    2011-01-01

    目的:观察侧脑室注射蛋白酶体抑制剂MG132对脑室室管膜下区(SVZ)神经干细胞(NSCs)增殖能力的影响,了解蛋白酶体对NSCs增殖潜能的调控作用,从而进一步探讨蛋白酶体在帕金森病(PD)等老年性疾病神经元损伤中的可能作用机制.方法:选90日龄健康BALB/c小鼠,左侧侧脑室注射10 μg MG132,于注射后3 d、7 d、14 d提取SVZ总蛋白,荧光酶标仪检测蛋白酶体活性.同时腹腔注射5-溴-2-脱氧尿嘧啶核苷(BrdU),BrdU免疫荧光染色标记NSCs,动态观察蛋白酶体活性改变对NSCs增殖能力的影响.另设溶剂对照组左侧侧脑室注射等剂量DMSO,进行上述实验.结果:侧脑室注射MG132 3 d、7 d后,SVZ蛋白酶体活性较DMSO对照组显著降低(P<0.05),同时SVZ BrdU+ NSCs也显著减少至21±4和22±3,与DMSO对照组相比差异显著(P<0.05).随着MG132注射时间延长,14 d后SVZ蛋白酶体活性恢复至正常水平(P>0.05),BrdU+ NSCs数量MG132组(82±4)与DMSO组(67±6)相比无显著差别(P>0.05).结论:应用蛋白酶体可逆性抑制剂MG132短时期内能显著抑制SVZ蛋白酶体活性,并且能够降低NSCs增殖能力,提示蛋白酶体活性与NSCs增殖潜能密切相关.%AIM: To investigate the role of proteasome in the degeneration of neuron in age - related diseases such as Parkinson disease ( PD ) by observing the effects of proteasome inhibitor MG132 on the proliferation of neural stem cells ( NSCs ) in the subventricular zone ( SVZ ).METHODS: Stereotaxic microinjection of proteasome inhibitor MG132 at a dose of 10 μg into the left lateral ventricle of 90 - day - old mice was performed.The control mice were received the same volume of DMSO into the left lateral ventricle.Three days, 7 days and 14 days after injection, the total proteins isolat from SVZ were subject to proteasome activity assay using the fluorescence microplate reader.Meanwhile, the mice were administered with 5 - bromo - 2' - deoxyuridine ( BrdU ) by

  3. Differentiation of neural stem cells isolated from subventricular zone and hippocampus of neonatal rats in serum-free medium%新生大鼠海马区及室管膜下区神经干细胞的诱导分化:无血清培养条件下观察

    Institute of Scientific and Technical Information of China (English)

    石德金; 郭英; 梁朝峰; 胡黎平; 李燕

    2007-01-01

    observe the characteristics of isolation, proliferation and differentiation of in vitro NSCs from subventricular zone (SVZ) and hippocampus of neonatal rats.DESIGN: Single-sample trial.SETTING: Department of Neurosurgery in the Third Affiliated Hospital of Sun Yat-sen University.MATERIALS: Ten SD rats aged 3 days, of either gender, were offered from the Experimental Animal Center of Sun Yat-sen University. Nestin antibody (rabbit-anti-rat), neurofilament (NF-200) antibody (rabbit-anti-rat), and glial fibrillary acidic protein (GFAP) antibody (mice-anti-rat) were all purchased from Sigma Company.METHODS: The experiment was carried out in the Laboratory of Histology and Embryology, Basic Medical College of Sun Yat-sen University from September to December in 2006. According to the ethical requirement, the serum-free DMEM/F12 medium containing basic fibroblast growth factor and epidermal growth factor was utilized to isolate and incubate NSCs from SVZ and hippocampus of neonatal rats. Then the proliferation and differentiation of NSCs in vitro were observed.MAIN OUTCOME MEASURES: Fluorescence immunocytochemistry was applied to detect the antigen of nestin expressed from NSCs, NF expressed from neuron cells and GFAP expressed from astrocytes. The differentiation of NSCs was identified.RESULTS: The cells isolated from SVZ and hippocampus of neonatal rats possessed the ability of proliferation and self-renewal. Through inverted microscope, nestin positive cells could be found in the cell clone sphere at passage 20 of cells. Cells induced to differentiate could express antigen of NF and GFAP by the attached cell clone sphere.CONCLUSION: The NSCs successfully isolated from SVZ and hippocampi of neonatal rats possess the ability of self-renewal, proliferation, and differentiation into neuron-like cells and astrocytes.

  4. Effects of N-methyl-D-aspartate Receptor Antagonist MK-801 on Expression of Glial Fibrillary Acidic Protein in the Subventricular Zone of Neonatal Rat%NMDA受体拮抗剂MK-801对新生大鼠室管膜下区胶质纤维酸性蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    李晓泉; 陈芳芳; 王伟; 来青伟; 耿德勤; 樊红彬

    2013-01-01

    Aim To investigate the effects of the N-methyl-D-aspartate(NMDA)-receptor antagonist MK801 on the expression of glial fibrillary acidic protein(GFAP) in the subventricular zone(SVZ) of neonatal rat.Methods 40 neonatal SD rats were assigned into two groups,a MK-801 group and a control group.Each group was respectively divided into four time points,including P7 d (postnatal 7 days),P14 d,P21 d and P28 d.Rats in the experiment group were intraperitoneally injected selective non-competitive NMDA receptor antagonist MK-801 (10 mg·kg1),while rats in the control group were intraperitoneally injected saline.Immunohistochemical staining was used to assay the number of GFAP-positive cells in the SVZ.Results ① In the control group,the number of GFAP-positive cells increased at P14 d,and the number of GFAP-positive cells reached maximum at P21 d,positive cells decreased significantly at 28 d.② Compared with the control group,the number of GFAP-positive cells reduced significantly at P 14 d (65.40 ± 6.11) and P21 d (239.60 ± 12.92),and the number of GFAP-positive cells increased significantly [P14 d(79.20 ± 5.26),P21 d(265.20 ± 7.40)](P<0.01),while the number of positive cells without obvious changes at P7 d and P28 d in the MK-801 group.Conclusion NMDA-receptor antagonist MK-801 could reduce the expression of GFAP in the SVZ,and inhibit the neural stem cells proliferation and differentiation.%目的 研究N-甲基-D-天冬氨酸(NMDA)受体拮抗剂MK-801对新生7d大鼠室管膜下区(SVZ)胶质纤维酸性蛋白(GFAP)表达的影响.方法 将40只新生SD大鼠分成对照组和MK-801组,各组按出生后口(P)时间点再随机分成4个亚组:P7d、P14d、P21 d、P28d组.新生大鼠均于生后第3天给药,MK-801组腹腔注射MK-801 10 mg·kg-1;对照组腹腔注射同量生理盐水.通过免疫组化学方法观察大鼠SVZ区GFAP阳性细胞数.结果 ①对照组GFAP阳性细胞数于P14 d开始增加,至P21 d达最大值;但P28 d时阳

  5. Adult neurogenesis in the four-striped mice (Rhabdomys pumilio)

    Institute of Scientific and Technical Information of China (English)

    Olatunbosun O Olaleye; Amadi O Ihunwo

    2014-01-01

    In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunos-taining conifrmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunore-active cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity.

  6. BDNF control of adult SVZ neurogenesis.

    Science.gov (United States)

    Bath, Kevin G; Akins, Michael R; Lee, Francis S

    2012-09-01

    The sensory processing of odorants is a dynamic process that requires plasticity at multiple levels. In the olfactory bulb (OB), inhibitory interneurons undergo lifelong replacement through a process known as adult neurogenesis. These newly born cells are incorporated in a learning-dependent fashion, a process which has led some to suggest this as a primary mechanism through which the OB retains a high degree of plasticity throughout life. A continued focus of researchers in this field has been to understand the molecular mechanisms controlling adult subventricular zone (SVZ) neurogenesis and the innate functional role of these cells. Brain-derived neurotrophic factor (BDNF) has been identified as a strong candidate molecule regulating adult OB neurogenesis. We review what is known regarding the functional role of newly born cells, highlight the role of BDNF in this process, and describe preliminary findings from our lab implicating BDNF in the process of selecting of newly born cells for survival.

  7. Strong natural selection on juveniles maintains a narrow adult hybrid zone in a broadcast spawner.

    Science.gov (United States)

    Prada, Carlos; Hellberg, Michael E

    2014-12-01

    Natural selection can maintain and help form species across different habitats, even when dispersal is high. Selection against inferior migrants (immigrant inviability) acts when locally adapted populations suffer high mortality on dispersal to unsuitable habitats. Habitat-specific populations undergoing divergent selection via immigrant inviability should thus show (1) a change in the ratio of adapted to nonadapted individuals among age/size classes and (2) a cline (defined by the environmental gradient) as selection counterbalances migration. Here we examine the frequencies of two depth-segregated lineages in juveniles and adults of a Caribbean octocoral, Eunicea flexuosa. Distributions of the two lineages in both shallow and deep environments were more distinct when inferred from adults than juveniles. Despite broad larval dispersal, we also found an extremely narrow hybrid zone (<100 m), with coincident clines for molecular and morphological characters of the host coral and its algal symbiont. Effective dispersal estimates derived from the hybrid zone are remarkably small (<20 m) for a broadcast spawner. The large selection coefficient against mismatched genotypes derived from cohort data is consistent with that from field transplant experiments. Narrow hybrid zones and limited effective dispersal may be a common outcome of long periods of postsettlement, prereproductive selection across steep ecological gradients. Strong diversifying selection provides a mechanism to explain the prevalence of depth-segregated sibling species in the sea.

  8. Experimental study of differentiatition of neural stem cells from anterior subventricular zone into GABAergic neurons%室管膜前下区神经干细胞诱导分化为γ-氨基丁酸能神经元的实验研究

    Institute of Scientific and Technical Information of China (English)

    辛志成; 周政; 严稽文

    2009-01-01

    目的 研究骨形成蛋白-2(bone morphogenetic protein-2,BMP2)及星形胶质细胞条件培养液(astrocyte-conditioned mediarn.ACM)在室管膜前下区(anterior subventricular zolle,SVZa)神经干细胞分化为γ-氨基丁酸(gamma-aminobutyric acid,GABA)能神经元中的作用.方法 体外培养SVZa神经干细胞,分为对照组、BMP2组、ACM组、BMP2+ACM组分别予以诱导分化,通过免疫组化和流式细胞技术分别检测各组SVZa神经干细胞分化后GAD67+细胞的比例.结果 各实验组的GAD67+细胞的比例均明显高于对照组,其中BMP2+ACM组尤其显著,差异有显著性(P<0.05).结论 BMP2及ACM可以促进SVZa神经干细胞向GABA能神经元分化,而且BMP2与ACM有正协同作用.

  9. Associations between active living-oriented zoning and no adult leisure-time physical activity in the U.S.

    Science.gov (United States)

    Leider, Julien; Chriqui, Jamie F; Thrun, Emily

    2017-02-01

    Nearly one-third of adults report no leisure-time physical activity (LTPA). Governmental and authoritative bodies recognize the role that community design through zoning code changes can play in enabling LTPA. This study examined the association between zoning and no adult LTPA in the U.S. This study was conducted between 2012 and 2016, with analyses occurring in 2015-2016. Zoning codes effective as of 2010 were compiled for jurisdictions located in the 495 most populous U.S. counties and were evaluated for pedestrian-oriented code reform zoning, 11 active living-oriented provisions (e.g., sidewalks, bike-pedestrian connectivity, mixed use, bike lanes) and a summated zoning scale (max=12). Individual-level LTPA data were obtained from the 2012 CDC Behavioral Risk Factor Surveillance System (BRFSS). County-aggregated, population-weighted zoning variables were constructed for linking to BRFSS. Log-log multivariate regressions (N=147,517 adults), controlling for individual and county characteristics and with robust standard errors clustered on county, were conducted to examine associations between zoning and no LTPA. Relative risks (RR) compared predicted lack of LTPA at 0% and 100% county-level population exposure to each zoning predictor. Zoning code reforms were associated with a 13% lower probability of no LTPA (RR: 0.87, 95% CI: 0.82-0.92). Except for crosswalks, all zoning provisions were associated with an 11-16% lower probability of no LTPA. Having all 12 zoning provisions was associated with a 22% lower probability of no LTPA (RR: 0.78, 95% CI: 0.72-0.83). The results suggest that active living-oriented zoning is a policy lever available to communities seeking to reduce rates of no LTPA.

  10. IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult SVZ niche.

    Science.gov (United States)

    Pereira, Leticia; Medina, Rebeca; Baena, Miguel; Planas, Anna M; Pozas, Esther

    2015-01-01

    The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult brains of mice and rats. Interferon gamma (IFNγ) has somewhat controversially been associated with SVZ progenitor proliferation and neurogenesis. The in vivo involvement of IFNγ in the physiology of the adult SVZ niche is not fully understood and its intracellular mediators are unknown. Here we show that IFNγ, through activation of its canonical signal transducer and activator of transcription 1 (STAT1) pathway, acts specifically on Nestin+ progenitors by decreasing both progenitor proliferation and the number of cycling cells. In addition, IFNγ increases the number of neuroblasts generated without shifting glial fate determination. The final result is deficient recruitment of newborn neurons to the olfactory bulb (OB), indicating that IFNγ-induced stimulation of neuronal differentiation does not compensate for its antiproliferative effect. We conclude that IFNγ signaling via STAT1 in the SVZ acts dually as an antiproliferative and proneurogenic factor, and thereby regulates neurogenesis in normal adult brains.

  11. Neurogenesis in the adult peripheral nervous system

    Institute of Scientific and Technical Information of China (English)

    Krzysztof Czaja; Michele Fornaro; Stefano Geuna

    2012-01-01

    Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.

  12. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Science.gov (United States)

    Cavaliere, Fabio; Benito-Muñoz, Monica; Matute, Carlos

    2016-01-01

    Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson's disease, and cerebral ischemia. PMID:27127518

  13. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere

    2016-01-01

    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  14. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Carina eFernandes

    2015-04-01

    Full Text Available Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.

  15. Lengthening of Insect Development on Bt Zone Results in Adult Emergence Asynchrony: Does It Influence the Effectiveness of the High Dose/Refuge Zone Strategy?

    Directory of Open Access Journals (Sweden)

    Jean-Claude Grégoire

    2012-11-01

    Full Text Available The “High Dose/Refuge” strategy (HD/R is the currently recommended Insect Resistance Management strategy (IRM to limit resistance development to Bacillus thuringiensis (Bt plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and in close proximity to a “Bt zone” expressing a high toxin concentration. One of the main assumptions is that enough susceptible adults mate with resistant insects. However, previous studies have suggested that the high toxin concentration produced by Bt plants induces slower insect development, creating an asynchrony in emergence between the refuge and the Bt zone and leading to assortative mating between adults inside each zone. Here, we develop a deterministic model to estimate the impact of toxin concentration, emergence asynchrony and refuge zone size on the effectiveness of the HD/R strategy. We conclude that emergence asynchrony only affects resistance when toxin concentration is high and resistance is recessive. Resistance develops more rapidly and survival of susceptible insects is higher at lower toxin concentration, but in such situations, resistance is insensitive to emergence asynchrony.

  16. Lengthening of insect development on Bt zone results in adult emergence asynchrony: does it influence the effectiveness of the high dose/refuge zone strategy?

    Science.gov (United States)

    Gryspeirt, Aiko; Grégoire, Jean-Claude

    2012-11-15

    The “High Dose/Refuge” strategy (HD/R) is the currently recommended Insect Resistance Management strategy (IRM) to limit resistance development to Bacillus thuringiensis (Bt) plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and in close proximity to a “Bt zone” expressing a high toxin concentration. One of the main assumptions is that enough susceptible adults mate with resistant insects. However, previous studies have suggested that the high toxin concentration produced by Bt plants induces slower insect development, creating an asynchrony in emergence between the refuge and the Bt zone and leading to assortative mating between adults inside each zone. Here, we develop a deterministic model to estimate the impact of toxin concentration, emergence asynchrony and refuge zone size on the effectiveness of the HD/R strategy. We conclude that emergence asynchrony only affects resistance when toxin concentration is high and resistance is recessive. Resistance develops more rapidly and survival of susceptible insects is higher at lower toxin concentration, but in such situations, resistance is insensitive to emergence asynchrony.

  17. New neurons clear the path of astrocytic processes for their rapid migration in the adult brain.

    Science.gov (United States)

    Kaneko, Naoko; Marín, Oscar; Koike, Masato; Hirota, Yuki; Uchiyama, Yasuo; Wu, Jane Y; Lu, Qiang; Tessier-Lavigne, Marc; Alvarez-Buylla, Arturo; Okano, Hideyuki; Rubenstein, John L R; Sawamoto, Kazunobu

    2010-07-29

    In the long-range neuronal migration of adult mammals, young neurons travel from the subventricular zone to the olfactory bulb, a long journey (millimeters to centimeters, depending on the species). How can these neurons migrate through the dense meshwork of neuronal and glial processes of the adult brain parenchyma? Previous studies indicate that young neurons achieve this by migrating in chains through astrocytic tunnels. Here, we report that young migrating neurons actively control the formation and maintenance of their own migration route. New neurons secrete the diffusible protein Slit1, whose receptor, Robo, is expressed on astrocytes. We show that the Slit-Robo pathway is required for morphologic and organizational changes in astrocytes that result in the formation and maintenance of the astrocytic tunnels. Through this neuron-glia interaction, the new neurons regulate the formation of the astrocytic meshwork that is needed to enable their rapid and directional migration in adult brain.

  18. Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviours

    Directory of Open Access Journals (Sweden)

    Lillian eGarrett

    2015-11-01

    Full Text Available Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ along the walls of the lateral ventricles and the subgranular zone (SGZ of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB - and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX promoter control were crossed with mice where diphtheria toxin A (DTA was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM, results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months and middle (from 10 months aged mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the tamoxifen treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.

  19. More Active Living-oriented County and Municipal Zoning is Associated with Increased Adult Leisure Time Physical Activity-United States, 2011.

    Science.gov (United States)

    Chriqui, Jamie F; Nicholson, Lisa M; Thrun, Emily; Leider, Julien; Slater, Sandy J

    2016-01-01

    Although zoning is recognized for its role in facilitating healthy communities, no study has examined whether active living-oriented zoning codes are associated with adult leisure time physical activity (PA). This study sought to fill this gap and hypothesized that adult leisure time PA would be greater in communities with more progressive zoning code reforms and more active living-oriented zoning. Zoning codes for 1,617 county and municipal jurisdictions located in 30 states (covering ~40% of the U.S. population) were evaluated for code reform zoning and 11 active living markers. County-aggregated zoning measures were created for linking with five adult PA behaviors obtained from the 2011 Behavioral Risk Factor Surveillance System controlling for individual and county sociodemographics. Zoning elements most associated with adult PA included requirements for mixed use, active and passive recreation, bike parking/street furniture, and bike-pedestrian trails/paths. This study provides new insights as to the role that zoning can play in facilitating adult PA.

  20. Wnt signaling in the regulation of adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Lorena eVarela-Nallar

    2013-06-01

    Full Text Available In the adult brain new neurons are continuously generated mainly in two regions, the subventricular zone of the lateral ventricles and the subgranular zone (SGZ in the hippocampal dentate gyrus. In the SGZ, radial neural stem cells give rise to granule cells that integrate into the hippocampal circuitry and are relevant for the plasticity of the hippocampus. Loss of neurogenesis impairs learning and memory, suggesting that this process is important for adult hippocampal function. Adult neurogenesis is tightly regulated by multiple signaling pathways, including the canonical Wnt/beta-catenin pathway. This pathway plays important roles during the development of neuronal circuits and in the adult brain it modulates synaptic transmission and plasticity. Here, we review current knowledge on the regulation of adult hippocampal neurogenesis by the Wnt/beta-catenin signaling cascade and the potential mechanisms involved in this regulation. Also we discuss the evidence supporting that the canonical Wnt pathway is part of the signaling mechanisms involved in the regulation of neurogenesis in different physiological conditions. Finally, some unsolved questions regarding the Wnt-mediated regulation of neurogenesis are discussed.

  1. Wnt signaling in the regulation of adult hippocampal neurogenesis

    Science.gov (United States)

    Varela-Nallar, Lorena; Inestrosa, Nibaldo C.

    2013-01-01

    In the adult brain new neurons are continuously generated mainly in two regions, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) in the hippocampal dentate gyrus. In the SGZ, radial neural stem cells (NSCs) give rise to granule cells that integrate into the hippocampal circuitry and are relevant for the plasticity of the hippocampus. Loss of neurogenesis impairs learning and memory, suggesting that this process is important for adult hippocampal function. Adult neurogenesis is tightly regulated by multiple signaling pathways, including the canonical Wnt/β-catenin pathway. This pathway plays important roles during the development of neuronal circuits and in the adult brain it modulates synaptic transmission and plasticity. Here, we review current knowledge on the regulation of adult hippocampal neurogenesis by the Wnt/β-catenin signaling cascade and the potential mechanisms involved in this regulation. Also we discuss the evidence supporting that the canonical Wnt pathway is part of the signaling mechanisms involved in the regulation of neurogenesis in different physiological conditions. Finally, some unsolved questions regarding the Wnt-mediated regulation of neurogenesis are discussed. PMID:23805076

  2. Adult Neurogenesis and Gliogenesis: Possible Mechanisms for Neurorestoration

    Science.gov (United States)

    Rusznák, Zoltán; Henskens, Willem; Schofield, Emma; Kim, Woojin S.

    2016-01-01

    The subgranular zone (SGZ) and subventricular zone (SVZ) are developmental remnants of the germinal regions of the brain, hence they retain the ability to generate neuronal progenitor cells in adult life. Neurogenesis in adult brain has an adaptive function because newly produced neurons can integrate into and modify existing neuronal circuits. In contrast to the SGZ and SVZ, other brain regions have a lower capacity to produce new neurons, and this usually occurs via parenchymal and periventricular cell genesis. Compared to neurogenesis, gliogenesis occurs more prevalently in the adult mammalian brain. Under certain circumstances, interaction occurs between neurogenesis and gliogenesis, facilitating glial cells to transform into neuronal lineage. Therefore, modulating the balance between neurogenesis and gliogenesis may present a new perspective for neurorestoration, especially in diseases associated with altered neurogenesis and/or gliogenesis, cell loss, or disturbed homeostasis of cellular constitution. The present review discusses important neuroanatomical features of adult neurogenesis and gliogenesis, aiming to explore how these processes could be modulated toward functional repair of the adult brain. PMID:27358578

  3. Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Kanako Nakaguchi

    2011-01-01

    Full Text Available Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

  4. 离体培养的生后大鼠脑室下层神经元前体细胞免疫细胞化学和形态学研究%IMMUNOCYTOCHEMIICAL AND MORPHOMETRICAL STUDY OF THE NEURONAL PRECURSOR CELLS DERIVED FROM THE SUBVENTRICULAR ZONE OF THE POSTNATAL RAT FOREBRAIN IN VITRO

    Institute of Scientific and Technical Information of China (English)

    高殿帅; 张凤真; 王德广; 周长福

    2000-01-01

    In order to investigate the chemical and morphornetrical properties of the neuronal precursor cells derived from thesubventricular zone(SVZ) of the postnatal rat forebrain in vitro. The cell-type specific antibodies were used for the immunocy-tochemical staining ,and the morphometric parameters which were the mean soma diameter and the ellipticity index (i. e. , thesmallest soma diameter divided by the largest soma diameter) of every SVZ-derived cell were measured for identifying the pheno-types of the SVZ cells in vitro. The experiment animals were SD rats (weights: 100~ 150 g), the SVZ cells derived from thepostnatal rats were cultured on poly-D-lysine-coated 24-well glass chamber slides in the Neurobasal Medium supplemented withB27 in 5% CO2 at 37 C. The following results were obtained.. At 1 day in vitro, almost all SVZ cells (〉90%) from the postna-tal rat forebrain expressed Tujl, an antibody that recognizes neuron-specific tubulin. Likewise, the preponderance of the SVZcells expressed the polysialylated neural cell adhesion molecule (PSA-N-CAM) ; The majority of the SVZ Tujl-positive cells cul-tured were the cells that had oval-shaped bodies with two short, unbranched processes protruded from every two poles, theirmean soma diameter were 8.42±1.03μm and their ellipticity index were 0.57±0.12. Meanwhile, there were approximately20% of the SVZ cells in culture that were sphere-shaped cells with mean soma diameter 7.20±l.04 μm , and it might be observed that these cells connected with one another. As the time in culture went on, these sphere-shaped SVZ-derived cells alsotransformed to oval-shaped ones as described above, but it could be observed that the cells were still connected in the processesof them. By 3 and 5 days in culture, the SVZ cells had larger cell somas (average diameter 9. 07±1.07 μm), and often consider-ably longer processes but still with few branches. Immunocytochemical staining revealed that the majority of the SVZ cells in cul

  5. Inducible and targeted deletion of the ERK5 MAP kinase in adult neurogenic regions impairs adult neurogenesis in the olfactory bulb and several forms of olfactory behavior.

    Directory of Open Access Journals (Sweden)

    Yung-Wei Pan

    Full Text Available Although adult-born neurons in the subventricular zone (SVZ and olfactory bulb (OB have been extensively characterized at the cellular level, their functional impact on olfactory behavior is still highly controversial with many conflicting results reported in the literature. Furthermore, signaling mechanisms regulating adult SVZ/OB neurogenesis are not well defined. Here we report that inducible and targeted deletion of erk5, a MAP kinase selectively expressed in the adult neurogenic regions of the adult brain, impairs adult neurogenesis in the SVZ and OB of transgenic mice. Although erk5 deletion had no effect on olfactory discrimination among discrete odorants in the habituation/dishabituation assay, it reduced short-term olfactory memory as well as detection sensitivity to odorants and pheromones including those evoking aggression and fear. Furthermore, these mice show impaired acquisition of odor-cued associative olfactory learning, a novel phenotype that had not been previously linked to adult neurogenesis. These data suggest that ERK5 MAP kinase is a critical kinase signaling pathway regulating adult neurogenesis in the SVZ/OB, and provide strong evidence supporting a functional role for adult neurogenesis in several distinct forms of olfactory behavior.

  6. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury.

  7. Peripheral nerve injury induces adult brain neurogenesis and remodelling.

    Science.gov (United States)

    Rusanescu, Gabriel; Mao, Jianren

    2017-02-01

    Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI-induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non-invasive neuroimaging techniques. Because neurogenesis-mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis-based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs.

  8. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    Science.gov (United States)

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  9. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  10. Pulse labeling and long-term tracing of newborn neurons in the adult subgranular zone

    Institute of Scientific and Technical Information of China (English)

    Xuewen Cheng; Yang Li; Ying Huang; Xiaoyan Feng; Guoping Feng; Zhi-Qi Xiong

    2011-01-01

    Research over the past decades has demonstrated that adult brain produces neural progenitor cells which proliferate and differentiate to newborn neurons that integrate into the existing circuit.However, detailed differentiation processes and underlying mechanisms of newly generated neurons are largely unknown due to the limitation of available methods for labeling and manipulating neural progenitor cells and newborn neurons. In this study, we designed a tightly controlled,noninvasive system based on Cre/loxP recombination to achieve long-term tracing and genetic manipulation of adult neurons in vivo. In this system, tamoxifen-inducible recomumase,CreERT2,was driven by BAC-based promoter of doublecortin(DCX,a marker of newborn neurons).By crossing this Cre line with reporter mouse, we found that newborn neurons in the dentate gyrus (DG) could be selectively pulse-labeled by tamoxifeninduced expression of yellow fluorescent protein(YFP).YFP-positive neurons were identified by coimmunostaining with cell type-specific markers and characterized by electrophysiological recording.Furthermore,analysis of the migration of these neurons showed that the majority of these labeled neurons migrated to the inner part of granule cell layer.Moreover,spine growth of inner molecular layer of newborn granule neurons takes a dynamic pattern of invert U-shape,in contrast to the wedge-shaped change in the outer molecular layer.Our transgenic tool provides an efficient way to selectively label and manipulate newborn neuron in adult mouse DG.

  11. c-jun is differentially expressed in embryonic and adult neural precursor cells.

    Science.gov (United States)

    Kawashima, Fumiaki; Saito, Kengo; Kurata, Hirofumi; Maegaki, Yoshihiro; Mori, Tetsuji

    2017-01-16

    c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.

  12. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.

  13. Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Tan Li

    Full Text Available Recent studies have led to the exciting idea that adult-born neurons in the olfactory bulb (OB may be critical for complex forms of olfactory behavior in mice. However, signaling mechanisms regulating adult OB neurogenesis are not well defined. We recently reported that extracellular signal-regulated kinase (ERK 5, a MAP kinase, is specifically expressed in neurogenic regions within the adult brain. This pattern of expression suggests a role for ERK5 in the regulation of adult OB neurogenesis. Indeed, we previously reported that conditional deletion of erk5 in adult neurogenic regions impairs several forms of olfactory behavior in mice. Thus, it is important to understand how ERK5 regulates adult neurogenesis in the OB. Here we present evidence that shRNA suppression of ERK5 in adult neural stem/progenitor cells isolated from the subventricular zone (SVZ reduces neurogenesis in culture. By contrast, ectopic activation of endogenous ERK5 signaling via expression of constitutive active MEK5, an upstream activating kinase for ERK5, stimulates neurogenesis. Furthermore, inducible and conditional deletion of erk5 specifically in the neurogenic regions of the adult mouse brain interferes with cell cycle exit of neuroblasts, impairs chain migration along the rostral migratory stream and radial migration into the OB. It also inhibits neuronal differentiation and survival. These data suggest that ERK5 regulates multiple aspects of adult OB neurogenesis and provide new insights concerning signaling mechanisms governing adult neurogenesis in the SVZ-OB axis.

  14. Communities on the move: Pedestrian-oriented zoning as a facilitator of adult active travel to work in the United States

    Directory of Open Access Journals (Sweden)

    Jamie Friedman Chriqui

    2016-04-01

    Full Text Available Background: Communities across the United States have been reforming their zoning codes to create pedestrian-friendly neighborhoods with increased street connectivity, mixed-use and higher density, open space, transportation infrastructure, and a traditional neighborhood structure. Zoning code reforms include new urbanist zoning such as the SmartCode, form-based codes, transects, transportation and pedestrian-oriented developments, and traditional neighborhood developments.Purpose: To examine the relationship of zoning code reforms and more active living-oriented zoning provisions with adult active travel to work via walking, biking, or by using public transit.Methods: Zoning codes effective as of 2010 were compiled for 3,914 municipal-level jurisdictions located in 471 counties and 2 consolidated cities in 48 states and the District of Columbia, and that collectively covered 72.9% of the U.S. population. Zoning codes were evaluated for the presence of code reform zoning and nine pedestrian-oriented zoning provisions (1=yes: sidewalks, crosswalks, bike-pedestrian connectivity, street connectivity, bike lanes, bike parking, bike-pedestrian trails/paths, mixed use development, and other walkability/pedestrian-orientation. A zoning scale reflected the number of provisions addressed (out of 10. Five continuous outcome measures were constructed using 2010-2014 American Community Survey municipal-level 5-year estimates to assess the percentage of workers: walking, biking, walking or biking, or taking public transit to work OR engaged in any active travel to work. Regression models controlled for municipal-level socioeconomic characteristics and a GIS-constructed walkability scale and were clustered on county with robust standard errors. Results: Adjusted models indicated that several pedestrian-oriented zoning provisions were statistically associated (p<.05 or lower with increased rates of walking, biking, or engaging in any active travel (walking

  15. The germinal zones of the basal ganglia but not the septum generate GABAergic interneurons for the cortex.

    Science.gov (United States)

    Rubin, Anna N; Alfonsi, Fabienne; Humphreys, Michael P; Choi, Christina K P; Rocha, Susana F; Kessaris, Nicoletta

    2010-09-08

    Cortical interneurons originate from subpallial precursors and migrate into the cortex during development. Using genetic lineage tracing in transgenic mice we examine the contribution of two germinal zones, the septum and the lateral ganglionic eminence/caudal ganglionic eminence (LGE/CGE) to interneurons of the cortex. We find that the septal neuroepithelium does not generate interneurons for the neocortex. There is, however, clear migration of cells from the LGE/CGE to the cortex. Comparison of the dynamics of cortical colonization by the two major cohorts of interneurons originating in the medial ganglionic eminence (MGE) and the LGE/CGE has shown differences in the timing of migration and initial route of entry into the cortex. LGE/CGE-derived interneurons enter the cortex later than the MGE-derived ones. They invade the cortex through the subventricular/intermediate zone route and only later disperse within the cortical plate and the marginal zone. During the first postnatal week MGE interneurons move extensively to acquire their laminar position within the cortical plate whereas LGE/CGE-derived cells remain largely within the upper layers of the cortex. The two populations intermingle in the adult cortex but have distinct neurochemical properties and different overall distributions. LGE/CGE-derived interneurons account for one third of the total GABAergic interneuron population in the adult cortex.

  16. [Autoradiographic investigations on postnatal proliferative activity of the telencephalic and diencephalic matrix-zones in the axolotl (Ambystoma mexicanum), with special references to the olfactory organ (author's transl)].

    Science.gov (United States)

    Richter, W; Kranz, D

    1981-01-01

    The localization and proliferative activity of the matrix-zones has been investigated in the telencephalon and in the diencephalon of 21 axolotls (Ambystoma mexicanum) by means of autoradiographs, after injection of tritiated thymidine at different stages of the postnatal life. There are no previous detailed autoradiographical reports on postnatal brain development in the axolotl. Matrix-zones (i.e. ventricular and subventricular zone) exist in the dorsal part and in the ventral part of the telencephalon, we have found these also in the diencephalon in the wall of the preoptic recessus and ventrally of the habenula. The quantitative part of this study indicates high values of the labeling-index in the early postnatal stages. Then, the labeling-index decreases, but also in 3 years old specimens labeled cells were observed in the matrix-zones of the telencephalon; therefore a few of proliferative capacity remains in the central nervous system of adult axolotls. Labeled cells were also found in the olfactory organ of early postnatal and adult axolotls; these are neuroblasts which have relevance for the regeneration of the forebrain.

  17. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    Science.gov (United States)

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  18. Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

    Directory of Open Access Journals (Sweden)

    Martin Regensburger

    2014-01-01

    Full Text Available In Parkinson’s disease (PD and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

  19. Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning

    Directory of Open Access Journals (Sweden)

    Matthew Valley

    2009-11-01

    Full Text Available Adult neurogenesis replenishes olfactory bulb (OB interneurons throughout the life of most mammals, yet during this constant fl ux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the subventricular zone (SVZ. Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral defi cit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local fi eld potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB.

  20. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    Science.gov (United States)

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-09-18

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

  1. Time-of-day-dependent enhancement of adult neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    So-ichi Tamai

    Full Text Available BACKGROUND: Adult neurogenesis occurs in specific regions of the mammalian brain such as the dentate gyrus of the hippocampus. In the neurogenic region, neural progenitor cells continuously divide and give birth to new neurons. Although biological properties of neurons and glia in the hippocampus have been demonstrated to fluctuate depending on specific times of the day, it is unclear if neural progenitors and neurogenesis in the adult brain are temporally controlled within the day. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that in the dentate gyrus of the adult mouse hippocampus, the number of M-phase cells shows a day/night variation throughout the day, with a significant increase during the nighttime. The M-phase cell number is constant throughout the day in the subventricular zone of the forebrain, another site of adult neurogenesis, indicating the daily rhythm of progenitor mitosis is region-specific. Importantly, the nighttime enhancement of hippocampal progenitor mitosis is accompanied by a nighttime increase of newborn neurons. CONCLUSIONS/SIGNIFICANCE: These results indicate that neurogenesis in the adult hippocampus occurs in a time-of-day-dependent fashion, which may dictate daily modifications of dentate gyrus physiology.

  2. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    Science.gov (United States)

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions.

  3. Polarized and Stage-Dependent Distribution of Immunoreactivity for Novel PDZ-Binding Protein Preso1 in Adult Neurogenic Regions

    Directory of Open Access Journals (Sweden)

    Eun Soo Lee

    2014-09-01

    Full Text Available BackgroundAdult neural stem cells have the potential for self-renewal and differentiation into multiple cell lineages via symmetric or asymmetric cell division. Preso1 is a recently identified protein involved in the formation of dendritic spines and the promotion of axonal growth in developing neurons. Preso1 can also bind to cell polarity proteins, suggesting a potential role for Preso1 in asymmetric cell division.MethodsTo investigate the distribution of Preso1, we performed immunohistochemistry with adult mouse brain slice. Also, polarized distribution of Preso1 was assessed by immunocytochemistry in cultured neural stem cells.ResultsImmunoreactivity for Preso1 (Preso1-IR was strong in the rostral migratory stream and subventricular zone, where proliferating transit-amplifying cells and neuroblasts are prevalent. In cultured neural stem cells, Preso1-IR was unequally distributed in the cell cytosol. We also observed the distribution of Preso1 in the subgranular zone of the hippocampal dentate gyrus, another neurogenic region in the adult brain. Interestingly, Preso1-IR was transiently observed in the nuclei of doublecortin-expressing neuroblasts immediately after asymmetric cell division.ConclusionOur study demonstrated that Preso1 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, and may play a significant role in cell differentiation via association with cell polarity machinery.

  4. Novel primate miRNAs co-evolved with ancient target genes in germinal zone specific expression patterns

    OpenAIRE

    Arcila, ML; Betizeau, M; Cambronne, XA; Guzman, E.; Doerflinger, N; F. Bouhallier; H. Zhou; Wu, B.; N. Rani; Bassett, DS; Borello, U.; Huissoud, C; Goodman, RH; Dehay, C.; Kosik, KS

    2014-01-01

    Major nonprimate-primate differences in corticogenesis include the dimensions, precursor lineages, and developmental timing of the germinal zones (GZs). microRNAs (miRNAs) of laser-dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including ventricular zone (VZ) and outer and inner subcompartments of the outer subventricular zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but abs...

  5. A subpial, transitory germinal zone forms chains of neuronal precursors in the rabbit cerebellum.

    Science.gov (United States)

    Ponti, Giovanna; Peretto, Paolo; Bonfanti, Luca

    2006-06-01

    Protracted neurogenesis occurs at different postnatal stages in different brain locations, whereby leading to site-specific adult neurogenesis in some cases. No spontaneous genesis of neurons occurs in the cerebellum after the postnatal genesis of granule cells from the external germinal layer (EGL), a transitory actively proliferating zone which is thought to be exhausted before puberty. Here, we show the protracted genesis of newly generated neuronal precursors in the cerebellar cortex of young rabbits, persisting beyond puberty. Neuroblasts generated within an actively proliferating subpial layer thus extending the postnatal EGL are arranged to form thousands of tangential chains reminiscent of those responsible for cell migration in the forebrain subventricular zone. These subpial chains cover the whole cerebellar surface from the 2nd to the 5th month of life, then disappearing after puberty. In addition, we describe the appearance of similar groups of cells at the end of granule cell genesis in the mouse cerebellum, here limited to the short period of EGL exhaustion (4-5 days). These results show common features do exist in the postnatal reorganization of secondary germinal layers of brain and cerebellum at specific stages, parallel to differences in the slowing down of cerebellar neurogenesis among mammalian species.

  6. The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice.

    Science.gov (United States)

    Muraille, E; Dassesse, D; Vanderwinden, J M; Cremer, H; Rogister, B; Erneux, C; Schiffmann, S N

    2001-01-01

    The germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their effects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identified Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2, SHIP2, has the potential to regulate neuronal development. Using in situ hybridization technique with multiple synthetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic stages and subventricular zones at latter stages of brain and spinal cord and in the sympathetic chain. No significant expression was seen in differentiated fields. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphery, large expression was detected in muscle and kidney and moderate expression in thyroid, pituitary gland, digestive system and bone. In the adult brain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior subventricular zone, the rostral migratory stream and the olfactory tubercle. SHIP2 was also detected in the choroid plexuses and the granular layer of the cerebellum. The specificity of SHIP2 expression in neural stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA signal in neural cell adhesion molecule (N-CAM)-deficient mice, which present an accumulation of progenitor cells in the anterior subventricular zone and the rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by western blotting in proliferating neurospheres in culture and its downregulation in non-proliferating differentiated neurospheres. In conclusion, the close correlation between

  7. Myricitrin induces antidepressant-like effects and facilitates adult neurogenesis in mice.

    Science.gov (United States)

    Meyer, Erika; Mori, Marco Aurélio; Campos, Alline Cristina; Andreatini, Roberto; Guimarães, Francisco Silveira; Milani, Humberto; de Oliveira, Rúbia Maria Weffort

    2017-01-01

    Myricitrin (MYR) is a natural flavonoid that inhibits nitric oxide (NO) transmission and has an atypical antipsychotic-like profile in animal models. Considering that several NO inhibitors exert antidepressant-like effects, the present study evaluated the antidepressant-like effect of MYR (3-30mg/kg) in the tail suspension test (TST). Because of the putative relationship between adult neurogenesis and antidepressant activity, we also assessed cell proliferation, survival, and differentiation in adult neurogenic niches, including the subgranular zone (SGZ) and subventricular zone (SVZ). Similar to the positive control imipramine (IMI; 10mg/kg), repeated treatment with 10mg/kg MIR but not acute treatment reduced immobility time in the TST, indicating an antidepressant-like effect. No effect on general motor activity was observed. Myricitrin also facilitated cell proliferation in the SGZ of the hippocampal dentate gyrus and SVZ. In the SGZ, MYR increased the number of doublecortin- and 5-bromo-2'-deoxyuridine/neuronal nuclei-positive cells. Our results suggest that MYR facilitates hippocampal neurogenesis, which might contribute to its antidepressant-like effect and atypical antipsychotic-like profile.

  8. 成年大鼠液压冲击脑损伤诱导室下区Nestin和GFAP的表达%The expression of Nestin and GFAP in adult rat subventricular zone following injury caused by moderate lateral fluid percussion

    Institute of Scientific and Technical Information of China (English)

    屈建强; 贺西京; 杨平林; 师蔚; 李浩鹏; 兰宾尚; 袁普卫; 王国毓; 刘亦恒

    2004-01-01

    目的应用免疫组织化学和免疫荧光双标技术结合激光共聚焦显微镜,观察脑损伤后不同时期室下区巢蛋白(Nestin)和胶质酸性纤维蛋白(GFAP)的表达及其细胞类型.方法用动液压冲击法建立动物模型,用LeicaQ500IW图像处理系统及免疫组化和免疫荧光双标法分析和显示不同时期(1、3、5d, 1、2、3、4、6、8周)Nestin和GFAP的表达变化.结果损伤24h后,室下区有大量Nestin和GFAP的表达,且激光共聚焦显微镜观察到有Nestin阳性突起与GFAP共存现象, 7d左右达到高峰,然后随着时间的推移其表达逐渐下降.正常组和假手术组,室下区也可见到Nestin和GFAP的表达,但与脑损伤组相比较低(P<0.05).结论脑损伤可诱导室下区Nestin和GFAP的表达, Nestin阳性突起与GFAP共存细胞可能具有干细胞特性,与神经元的修复有关.

  9. Absent or low rate of adult neurogenesis in the hippocampus of bats (Chiroptera.

    Directory of Open Access Journals (Sweden)

    Irmgard Amrein

    Full Text Available Bats are the only flying mammals and have well developed navigation abilities for 3D-space. Even bats with comparatively small home ranges cover much larger territories than rodents, and long-distance migration by some species is unique among small mammals. Adult proliferation of neurons, i.e., adult neurogenesis, in the dentate gyrus of rodents is thought to play an important role in spatial memory and learning, as indicated by lesion studies and recordings of neurons active during spatial behavior. Assuming a role of adult neurogenesis in hippocampal function, one might expect high levels of adult neurogenesis in bats, particularly among fruit- and nectar-eating bats in need of excellent spatial working memory. The dentate gyrus of 12 tropical bat species was examined immunohistochemically, using multiple antibodies against proteins specific for proliferating cells (Ki-67, MCM2, and migrating and differentiating neurons (Doublecortin, NeuroD. Our data show a complete lack of hippocampal neurogenesis in nine of the species (Glossophaga soricina, Carollia perspicillata, Phyllostomus discolor, Nycteris macrotis, Nycteris thebaica, Hipposideros cyclops, Neoromicia rendalli, Pipistrellus guineensis, and Scotophilus leucogaster, while it was present at low levels in three species (Chaerephon pumila, Mops condylurus and Hipposideros caffer. Although not all antigens were recognized in all species, proliferation activity in the subventricular zone and rostral migratory stream was found in all species, confirming the appropriateness of our methods for detecting neurogenesis. The small variation of adult hippocampal neurogenesis within our sample of bats showed no indication of a correlation with phylogenetic relationship, foraging strategy, type of hunting habitat or diet. Our data indicate that the widely accepted notion of adult neurogenesis supporting spatial abilities needs to be considered carefully. Given their astonishing longevity, certain bat

  10. Disruption of adult neurogenesis in the olfactory bulb affects social interaction but not maternal behavior

    Directory of Open Access Journals (Sweden)

    Claudia E Feierstein

    2010-12-01

    Full Text Available Adult-born neurons arrive to the olfactory bulb and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of factors, notably by instances related to reproductive behavior, such as exposure to mating partners, pregnancy and lactation, and exposure to offspring. To study the contribution of olfactory neurogenesis to maternal behavior and social recognition, here we selectively disrupted olfactory bulb neurogenesis using focal irradiation of the subventricular zone in adult female mice. We show that reduction of olfactory neurogenesis results in an abnormal social interaction pattern with male, but not female, conspecifics; we suggest that this effect could result from inability to detect or discriminate male odors and could therefore have implications for the recognition of potential mating partners. Disruption of olfactory bulb neurogenesis, however, neither impaired maternal-related behaviors, nor did it affect the ability of mothers to discriminate their own progeny from others.

  11. Epigenetic Activation of Neuronal Gene Expression by JMJD3 is Required for Postnatal and Adult Brain Neurogenesis

    Science.gov (United States)

    Park, Dae Hwi; Hong, Sung Jun; Salinas, Ryan D.; Liu, Siyuan John; Sun, Shawn W.; Sgualdino, Jacopo; Testa, Giuseppe; Matzuk, Martin M.; Iwamori, Naoki; Lim, Daniel A.

    2014-01-01

    SUMMARY The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis from adult subventricular zone (SVZ) NSCs. JMJD3 is upregulated in neuroblasts, and Jmjd3-deletion targeted to SVZ NSCs in both developing and adult mice impairs neuronal differentiation. JMJD3 regulates neurogenic gene expression via interaction at not only promoter regions, but also neurogenic enhancer elements. JMJD3 localizes at neural enhancers genome-wide in embryonic brain, and in SVZ NSCs, JMJD3 regulates the I12b enhancer of Dlx2. In Jmjd3-deleted SVZ cells, I12b remains enriched with H3K27me3, and Dlx2-dependent neurogenesis fails. These findings support a model in which JMJD3 and the poised state of key transcriptional regulatory elements comprise an epigenetic mechanism that enables the activation of neurogenic gene expression in adult NSCs throughout life. PMID:25176653

  12. Activation of Neuronal Gene Expression by the JMJD3 Demethylase Is Required for Postnatal and Adult Brain Neurogenesis

    Directory of Open Access Journals (Sweden)

    Dae Hwi Park

    2014-09-01

    Full Text Available The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs in the adult mammalian brain are poorly understood. Here, we show that JMJD3, a histone H3 lysine 27 (H3K27 demethylase, acts as a critical activator of neurogenesis from adult subventricular zone (SVZ NSCs. JMJD3 is upregulated in neuroblasts, and Jmjd3 deletion targeted to SVZ NSCs in both developing and adult mice impairs neuronal differentiation. JMJD3 regulates neurogenic gene expression via interaction at not only promoter regions but also neurogenic enhancer elements. JMJD3 localizes at neural enhancers genome-wide in embryonic brain, and in SVZ NSCs, JMJD3 regulates the I12b enhancer of Dlx2. In Jmjd3-deleted SVZ cells, I12b remains enriched with H3K27me3 and Dlx2-dependent neurogenesis fails. These findings support a model in which JMJD3 and the poised state of key transcriptional regulatory elements comprise an epigenetic mechanism that enables the activation of neurogenic gene expression in adult NSCs throughout life.

  13. Pedestrian-oriented zoning is associated with reduced income and poverty disparities in adult active travel to work, United States.

    Science.gov (United States)

    Chriqui, Jamie F; Leider, Julien; Thrun, Emily; Nicholson, Lisa M; Slater, Sandy J

    2017-02-01

    Active travel to work can provide additional minutes of daily physical activity. While the literature points to the relationship between zoning, equity and socioeconomic status, and physical activity, no study has quantitatively explored these connections. This study examined whether zoning may help to moderate any income and poverty inequities in active travel and taking public transit to work. Research was conducted between May 2012 and June 2015. Zoning data were compiled for 3914 jurisdictions covering 45.45% of the U.S. population located in 471 of the most populous U.S. counties and 2 consolidated cities located in 48 states and the District of Columbia. (Sensitivity analyses also captured unincorporated areas which, with the municipalities, collectively covered ~72% of the U.S.

  14. Assessment of hematological profiles of adult male athletes from two different air pollutant zones of West Bengal, India.

    Science.gov (United States)

    Das, Paulomi; Chatterjee, Pinaki

    2015-01-01

    Health effects from air pollution are severe concern of today's world. The study was undertaken to assess the effects of air pollution on hematological profiles of trained and untrained males of West Bengal. The sample consisted of 60 sprinters, 60 footballers, and 120 untrained males, subdivided into two groups from two zones, namely, Tollygunge and Sonarpur. Suspended particulate matter (SPM), respirable particulate matter (RPM), oxides of sulfur (SOx), and oxides of nitrogen (NOx) of ambient air were monitored for both zones. Height and weight of all the subjects were measured. Venous blood sample was drawn from the cubital vein, and the red blood cell count (TC), packed cell volume (PCV), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) were determined by standard methods. Results revealed that SPM, RPM, SOx, and NOx concentrations were significantly higher in the Tollygunge area than Sonarpur. TC, PCV, and Hb concentration of untrained males were significantly higher than footballers in both regions but no significant difference were observed when compared with sprinters, except the Hb concentration in the Tollygunge zone. On the other hand, all hematological parameters of both trained and untrained males were significantly higher in the Sonarpur area than Tollygunge. It was concluded that environmental air pollutants might influence hematological profile adversely both in trained and sedentary males. However, further investigation in this area is needed.

  15. Exosomes as novel regulators of adult neurogenic niches

    Directory of Open Access Journals (Sweden)

    Luis Federico Batiz

    2016-01-01

    Full Text Available Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ of the dentate gyrus (DG in the hippocampus, and the sub-ventricular zone (SVZ of the lateral ventricles. SGZ newborn neurons are destined to the granular cell layer of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb. The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs, which reside in a unique and specialized microenvironment known as neurogenic niche. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs. EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs, proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult

  16. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

    Directory of Open Access Journals (Sweden)

    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  17. Spatiotemporal expression patterns of Pax6 in the brain of embryonic, newborn, and adult mice.

    Science.gov (United States)

    Duan, Deyi; Fu, Yuhong; Paxinos, George; Watson, Charles

    2013-03-01

    The transcription factor Pax6 has been reported to specify neural progenitor cell fates during development and maintain neuronal commitments in the adult. The spatiotemporal patterns of Pax6 expression were examined in sagittal and horizontal sections of the embryonic, postnatal, and adult brains using immunohistochemistry and double immunolabeling. The proportion of Pax6-immunopositive cells in various parts of the adult brain was estimated using the isotropic fractionator methodology. It was shown that at embryonic day 11 (E11) Pax6 was robustly expressed in the proliferative neuroepithelia of the ventricular zone in the forebrain and hindbrain, and in the floor and the mesencephalic reticular formation (mRt) in the midbrain. At E12, its expression emerged in the nucleus of the lateral lemniscus in the rhombencephalon and disappeared from the floor of the midbrain. As neurodevelopment proceeds, the expression pattern of Pax6 changes from the mitotic germinal zone in the ventricular zone to become extensively distributed in cell groups in the forebrain and hindbrain, and the expression persisted in the mRt. The majority of Pax6-positive cell groups were maintained until adult life, but the intensity of Pax6 expression became much weaker. Pax6 expression was maintained in the mitotic subventricular zone in the adult brain, but not in the germinal region dentate gyrus in the adult hippocampus. There was no obvious colocalization of Pax6 and NeuN during embryonic development, suggesting Pax6 is found primarily in developing progenitor cells. In the adult brain, however, Pax6 maintains neuronal features of some subtypes of neurons, as indicated by 97.1% of Pax6-positive cells co-expressing NeuN in the cerebellum, 40.7% in the olfactory bulb, 38.3% in the cerebrum, and 73.9% in the remaining brain except the hippocampus. Differentiated tyrosine hydroxylase (TH) neurons were observed in the floor of the E11 midbrain where Pax6 was also expressed, but no obvious

  18. Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

    Institute of Scientific and Technical Information of China (English)

    Tomoko Kuwabara; Makoto Asashima

    2012-01-01

    Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

  19. Inducible expression of noggin selectively expands neural progenitors in the adult SVZ

    Directory of Open Access Journals (Sweden)

    M. Morell

    2015-01-01

    Full Text Available Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA. In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.

  20. Distribution of Müller stem cells within the neural retina: evidence for the existence of a ciliary margin-like zone in the adult human eye.

    Science.gov (United States)

    Bhatia, Bhairavi; Singhal, Shweta; Lawrence, Jean M; Khaw, Peng T; Limb, G Astrid

    2009-09-01

    Much interest has been generated by the identification of neural stem cells in the human neural retina and ciliary body. However, it is not clear whether stem cells identified in these ocular compartments are of the same origin or whether they ontogenically derive from different cell populations. This study examined the in situ anatomical distribution of these cells within the neural retina and ciliary body, as well as their ability to proliferate in response to EGF. Human retinae and ciliary body were examined for co-expression of Nestin, cellular retinaldehyde binding (CRALBP) or Vimentin, and the stem cell markers SOX2, CHX10, NOTCH1 and SHH. Retinal explants were cultured with epidermal growth factor (EGF) to assess retinal cell proliferation. Intense Nestin and CRALBP staining was observed in the neural retinal margin, where cells formed bundles of spindle cells (resembling glial cells) that lacked lamination and co-stained for SOX2, CHX10 and SHH. This staining differentiated the neural retina from the ciliary epithelium, which expressed SOX2, CHX10 and NOTCH1 but not Nestin or CRALBP. Nestin and CRALBP expression decreased towards the posterior retina, where it anatomically identified a population of Müller glia. All Vimentin positive Müller glia co-stained for SOX2, but only few Vimentin positive cells expressed Nestin and SOX2. Cells of the retinal margin and the inner nuclear layer (INL), where the soma of Müller glia predominate, re-entered the cell cycle upon retinal explant culture with EGF. Lack of lamination and abundance of Müller glia expressing stem cell markers in the marginal region of the adult human retina resemble the ciliary marginal zone (CMZ) of fish and amphibians. The findings that cells in this CM-like zone, as well in the inner nuclear layer proliferate in response to EGF suggest that the adult human retina has regenerative potential. Identification of factors that may promote retinal regeneration in the adult human eye would

  1. Prenatal Activation of Toll-Like Receptor-4 Dampens Adult Hippocampal Neurogenesis in An IL-6 Dependent Manner

    Science.gov (United States)

    Mouihate, Abdeslam

    2016-01-01

    Prenatal immune challenge has been associated with alteration in brain development and plasticity that last into adulthood. We have previously shown that prenatal activation of toll-like receptor 4 by lipopolysaccharide (LPS) induces IL-6-dependent STAT-3 signaling pathway in the fetal brain. Whether this IL-6-dependent activation of fetal brain results in long lasting impact in brain plasticity is still unknown. Furthermore, it has been shown that prenatal LPS heightens the hypothalamic–pituitary–adrenal (HPA) response in adulthood. In the present study we tested whether LPS administration during pregnancy affects neurogenesis in adult male offspring. Because corticosterone, the end-product of HPA axis activity in rats, alters neurogenesis we tested whether this enhanced HPA axis responsiveness in adult male offspring played a role in the long lasting impact of LPS on neurogenesis during adulthood. Pregnant rats were given either LPS, or LPS and an IL-6 neutralizing antibody (IL-6Ab). The newly born neurons were monitored in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus of adult male offspring by monitoring doublecortin and T-box brain protein-2 expression: two well-established markers of newly born neurons. Prenatal LPS decreased the number of newly born neurons in the DG, but not in the SVZ of adult offspring. This decreased number of newly born neurons in the DG was absent when IL-6Ab was co-injected with LPS during pregnancy. Furthermore, administration of a corticosterone receptor blocker, RU-486, to adult offspring blunted the prenatal LPS induced decrease in newly born neurons in the DG. These data suggest that maternally triggered IL-6 plays a crucial role in the long lasting impact of LPS on adult neurogenesis. PMID:27445700

  2. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  3. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Science.gov (United States)

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  4. SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.

    Science.gov (United States)

    Zhu, Chang; Yao, Wen-Long; Tan, Wei; Zhang, Chuan-Han

    2017-02-15

    Evidence has shown that stromal cell-derived factor (SDF-1/CXCL12) plays an important role in maintaining adult neural progenitor cells (NPCs). SDF-1 is also known to enhance recovery by recruiting NPCs to damaged regions and recent studies have revealed that SDF-1α exhibits pleiotropism, thereby differentially affecting NPC subpopulations. In this study, we investigated the role of SDF-1 in in vitro NPC self-renewal, proliferation and differentiation, following treatment with different concentrations of SDF-1 or a CXCR4 antagonist, AMD3100. We observed that AMD3100 inhibited the formation of primary neurospheres. However, SDF-1 and AMD3100 exhibited no effect on proliferation upon inclusion of growth factors in the media. Following growth factor withdrawal, AMD3100 and SDF-1 treatment resulted in differential effects on NPC proliferation. SDF-1, at a concentration of 500ng/ml, resulted in an increase in the relative proportion of oligodendrocytes following growth factor withdrawal-induced differentiation. Using CXCR4 knockout mice, we observed that SDF-1 affected NPC proliferation in the sub-ventricular zone (SVZ). We also investigated the occurrence of differential CXCR4 expression at different stages during lineage progression. These results clearly indicate that signaling interactions between SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.

  5. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  6. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  7. Biomaterial microenvironments to support the generation of new neurons in the adult brain.

    Science.gov (United States)

    Conway, Anthony; Schaffer, David V

    2014-05-01

    Neural stem cells (NSC) in two regions of the adult mammalian brain--the subventricular zone (SVZ) and hippocampus--continuously generate new neurons, enabled by a complex repertoire of factors that precisely regulate the activation, proliferation, differentiation, and integration of the newborn cells. A growing number of studies also report low-level neurogenesis in regions of the adult brain outside these established neurogenic niches--potentially via NSC recruitment or activation of local, quiescent NSCs--under perturbations such as ischemia, cell death, or viral gene delivery of proneural growth factors. We have explored whether implantation of engineered biomaterials can stimulate neurogenesis in normally quiescent regions of the brain. Specifically, recombinant versions of factors found within the NSC microenvironment, Sonic hedgehog, and ephrin-B2 were conjugated to long polymers, thereby creating highly bioactive, multivalent ligands that begin to emulate components of the neurogenic niche. In this engineered biomaterial microenvironment, new neuron formation was observed in normally non-neurogenic regions of the brain, the striatum, and the cortex, and combining these multivalent biomaterials with stromal cell-derived factor-1α increased neuronal commitment of newly divided cells seven- to eightfold in these regions. Additionally, the decreased hippocampal neurogenesis of geriatric rodents was partially rescued toward levels of young animals. We thus demonstrate for the first time de novo neurogenesis in both the cortex and striatum of adult rodents stimulated solely by delivery of synthetic biomaterial forms of proteins naturally found within adult neurogenic niches, offering the potential to replace neurons lost in neurodegenerative disease or injury as an alternative to cell implantation.

  8. EXPERIMENTAL STUDY ON PLASTICITY OF PROLIFERATED NEURAL STEM CELLS IN ADULT RATS AFTER CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Ren-zhi Wang; Zhi-gang Lian; Yang Song; Yong Yao

    2006-01-01

    Objective To investigate whether there is endogenous neural stem cell proliferation and whether these proliferated neural stem cells represent neural plasticity in the adult rats after cerebral infarction.Methods Cerebral infarction models of rats were established and the dynamic expression of bromodeoxyuridine (BrdU), BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark dividing neural stem cells. PSA-NCAM was used to mark the plasticity of neural stem cells.Results Compared with controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased significantly at 1st day after cerebral infarction (P<0.05), reached maximum at 7th day, decreased markedly at 14th day, but it was still elevated compared with that of the controls (P<0.05). The number of BrdU-labeled with PSA-NCAM-positive cells increased significantly at 7th day (P<0.05 ), reached maximum at 14th day,markedly decreased at 28th day, but it was still elevated compared with that of the controls (P<0.05). It was equal to 60% of the number of BrdU-positive cells in the same period.Conclusion Cerebral infarction may stimulate the proliferation of endogenous neural stem cells in situ and most proliferated neural stem cells represent neural plasticity.

  9. The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.

    Science.gov (United States)

    Fiorelli, Roberto; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose-Manuel; Raineteau, Olivier

    2013-12-01

    Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties.

  10. A comparative analysis of intraperitoneal versus intracerebroventricular administration of bromodeoxyuridine for the study of cell proliferation in the adult rat brain.

    Science.gov (United States)

    Cifuentes, M; Pérez-Martín, M; Grondona, J M; López-Ávalos, M D; Inagaki, N; Granados-Durán, P; Rivera, P; Fernández-Llebrez, P

    2011-10-15

    Bromodeoxyuridine (BrdU) is the most widely used marker to detect proliferative cells in the adult brain. Here we analyse whether the route of administration of the tracer influences the number of labelled cells. For the intraperitoneal (ip) administration of BrdU, we performed two daily injections during 7 days, and for an intracerebroventricular (icv) delivery, it was continuously infused into one lateral ventricle for a 7 days period as well. After ip administration, cells labelled with BrdU were seen in the subventricular zone of the striatal wall of the lateral ventricle, the hippocampus and the neurohemal circumventricular organs. Also, the habenula and large myelinated tracts, such as the fornix and the corpus callosum, showed many BrdU-positive nuclei. Labelled nuclei were scarce in the parenchymal regions of the rest of the brain. In contrast, a significant increase in the number of BrdU-positive nuclei was observed in the parenchyma of the periventricular zones after icv administration of the marker, thus showing a greater availability of the tracer when it was administered directly into the ventricular cerebrospinal fluid. We suggest that the availability of BrdU in the vicinity of proliferating cells may depend on the permeability of the brain vessels to nucleosides in each location. By using double immunocytochemistry we found that neurons, astrocytes, oligodendrocytes, tanycytes and microglia had incorporated the tracer, demonstrating their proliferation capacity.

  11. O efeito da metanfetamina na neurogénese da zona subventricular: morte celular, proliferação e diferenciação = The effect of methamphetamine on subventricular zone neurogenesis: cell death, proliferation and differentiation

    OpenAIRE

    Bento, Ana Rita das Neves Lagarto

    2009-01-01

    A metanfetamina é um psicoestimulante muito tóxico e viciante consumido no mundo inteiro, sendo a segunda droga mais consumida a seguir à cannabis. Os consumidores de metanfetamina demonstram alterações significativas na função e na estrutura do cérebro. Além disso, o défice de memória frequentemente observado nos consumidores de metanfetamina sugere que, para além do seu efeito tóxico, a metanfetamina poderá alterar a neurogénese. A produção de novos neurónios ocorre no cér...

  12. Field observations of climbing behavior and seed predation by adult ground beetles (Coleoptera: Carabidae) in a lowland area of the temperate zone.

    Science.gov (United States)

    Sasakawa, Kôji

    2010-10-01

    Granivory is a specialized food habit in the predominantly carnivorous beetle family Carabidae. Most studies of carabid granivory have been conducted under laboratory conditions; thus, our knowledge of the feeding ecology of granivorous carabids in the field is insufficient. I conducted field observations of climbing behavior and seed predation by adult carabids in a lowland area of eastern Japan, from early October to late November in 2008. This is the first systematic field observation of the feeding ecology of granivorous carabids in the temperate zone. In total, 176 carabid individuals of 11 species were observed, with 108 individuals feeding on plant seeds/flowers. Each carabid species was primarily observed feeding on a particular plant species. Frequently observed combinations were: Amara gigantea Motschulsky on Humulus scandens (Loureiro) Merrill (Moraceae) seed, Amara lucens Baliani on Artemisia indica Willdenow (Asteraceae) flower, and Amara macronota (Solsky) and Harpalus (Pseudoophonus) spp. on Digitaria ciliaris (Retzius) Koeler (Poaceae) seed. In all but one species, the sex ratio of individuals observed feeding was female-biased. In Am. gigantea and Am. macronota, a larger proportion of females than males ate seeds. In the three Amara species, copulations on plants, with the female feeding on its seeds/flowers, were often observed. These observations may indicate that, whereas females climb onto plants to feed on seeds, males climb to seek females for copulation rather than forage. Because granivorous carabids play important roles as weed-control agents in temperate agro-ecosystems, the present results would provide valuable basic information for future studies on this subject.

  13. Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

    Science.gov (United States)

    Capilla-Gonzalez, Vivian; Gil-Perotin, Sara; Ferragud, Antonio; Bonet-Ponce, Luis; Canales, Juan Jose; Garcia-Verdugo, Jose Manuel

    2012-01-01

    Background Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. Methodology/Principal Findings 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. Conclusions/Significance The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits. PMID:22238669

  14. A comparison of epithelial and neural properties in progenitor cells derived from the adult human ciliary body and brain.

    Science.gov (United States)

    Moe, Morten C; Kolberg, Rebecca S; Sandberg, Cecilie; Vik-Mo, Einar; Olstorn, Havard; Varghese, Mercy; Langmoen, Iver A; Nicolaissen, Bjørn

    2009-01-01

    Cells isolated from the ciliary body (CB) of the adult human eye possess properties of retinal stem/progenitor cells and can be propagated as spheres in culture. As these cells are isolated from a non-neural epithelium which has neuroepithelial origin, they may have both epithelial and neural lineages. Since it is the properties of neural progenitor cells that are sought after in a future scenario of autotransplantation, we wanted to directly compare human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized neural stem cell niche in the CNS of adults. The CB epithelium was dissected from donor eyes (n = 8). Biopsies from the ventricular wall were harvested during neurosurgery due to epilepsy (n = 7). CB and SVZ tissue were also isolated from Brown Norwegian rats. Dissociated single cells were cultivated in a sphere-promoting medium and passaged every 10-30 days. Fixed spheres were studied by immunohistochemistry, quantitative RT-PCR and scanning/transmission electron microscopy. We found that both CB and SVZ spheres contained a mixed population of cells embedded in extracellular matrix. CB spheres, in contrast to SVZ neurospheres, contained pigmented cells with epithelial morphology that stained for cytokeratins (3/12 + 19), were connected through desmosomes and tight-junctions and produced PEDF. Markers of neural progenitors (nestin, Sox-2, GFAP) were significantly lower expressed in human CB compared to SVZ spheres, and nestin positive cells in the CB spheres also contained pigment. There was higher expression of EGF and TGF-beta receptors in human CB spheres, and a comparative greater activation of the canonical Wnt pathway. These results indicate that adult human CB spheres contain progenitor cells with epithelial properties and limited expression of neural progenitor markers compared to CNS neurospheres. Further studies mapping the regulation between epithelial and neural properties in the adult human

  15. Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

    Directory of Open Access Journals (Sweden)

    Michael R Foret

    2014-07-01

    Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

  16. Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.

    Directory of Open Access Journals (Sweden)

    Vivian Capilla-Gonzalez

    Full Text Available BACKGROUND: Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU, a N-nitroso compound (NOC found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ, the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG, and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test and a deficit in spatial memory (Barnes maze performance, two functions primarily related to the SVZ and the DG regions, respectively. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits.

  17. Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb.

    Science.gov (United States)

    Wu, Jyun-Han; Han, Yueh-Ting; Yu, Jenn-Yah; Wang, Tsu-Wei

    2013-08-01

    Pheromones from urine of unfamiliar conspecific male animals can reinitiate a female's estrus cycle to cause pregnancy block through the vomeronasal organ (VNO)-accessory olfactory bulb (AOB)-hypothalamic pathway. This phenomenon is called the Bruce effect. Pheromones from the mate of the female, however, do not trigger re-entrance of the estrus cycle because an olfactory memory toward its mate is formed. The activity of the VNO-AOB-hypothalamic pathway is negatively modulated by GABAergic granule cells in the AOB. Since these cells are constantly replenished by neural stem cells in the subventricular zone (SVZ) of the lateral ventricle throughout adulthood and adult neurogenesis is required for mate recognition and fertility, we tested the hypothesis that pheromones from familiar and unfamiliar males may have different effects on adult AOB neurogenesis in female mice. When female mice were exposed to bedding used by a male or lived with one, cell proliferation and neuroblast production in the SVZ were increased. Furthermore, survival of newly generated cells in the AOB was enhanced. This survival effect was transient and mediated by norepinephrine. Interestingly, male bedding-induced newborn cell survival in the AOB but not cell proliferation in the SVZ was attenuated when females were subjected to bedding from an unfamiliar male. Our results indicate that male pheromones from familiar and unfamiliar males exert different effects on neurogenesis in the adult female AOB. Given that adult neurogenesis is required for reproductive behaviors, these divergent pheromonal effects may provide a mechanism for the Bruce effect. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 632-645, 2013.

  18. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    Science.gov (United States)

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis.

  19. Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis.

    Science.gov (United States)

    Kronenberg, Golo; Gertz, Karen; Baldinger, Tina; Kirste, Imke; Eckart, Sarah; Yildirim, Ferah; Ji, Shengbo; Heuser, Isabella; Schröck, Helmut; Hörtnagl, Heide; Sohr, Reinhard; Djoufack, Pierre Chryso; Jüttner, René; Glass, Rainer; Przesdzing, Ingo; Kumar, Jitender; Freyer, Dorette; Hellweg, Rainer; Kettenmann, Helmut; Fink, Klaus Benno; Endres, Matthias

    2010-03-03

    Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis.

  20. Adult human brain neural progenitor cells (NPCs and fibroblast-like cells have similar properties in vitro but only NPCs differentiate into neurons.

    Directory of Open Access Journals (Sweden)

    Thomas In-Hyeup Park

    Full Text Available The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia, and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs. These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting Ah

  1. Scorpion venom heat-resistant peptide (SVHRP enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Scorpion venom heat-resistant peptide (SVHRP is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM-positive immature neurons in the subventricular zone (SVZ and subgranular zone (SGZ of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF but not nerve growth factor (NGF or glial cell line-derived neurotrophic factor (GDNF was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values

  2. Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Wang, Tao; Wang, Shi-Wei; Zhang, Yue; Wu, Xue-Fei; Peng, Yan; Cao, Zhen; Ge, Bi-Ying; Wang, Xi; Wu, Qiong; Lin, Jin-Tao; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2014-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU)-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.

  3. A key to the adult Costa Rican “helicopter” damselflies (Odonata: Pseudostigmatidae) with notes on their phenology and life zone preferences

    OpenAIRE

    Hedström, Ingemar; Sahlén, Göran

    2015-01-01

    We present a key to the Costa Rican species of Pseudostigmatidae, comprising three genera with the following species: Megaloprepus caerulatus, Mecistogaster linearis, M. modesta, M. ornata and Pseudostigma aberrans. Pseudostigma accedens, which may occur in the region, is also included. For each species we give a brief account of morphology, phenology and life zone preferences, including distributional maps based on more than 270 records. These are not all of the known specimens from the area...

  4. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    Science.gov (United States)

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  5. Effect of a antisense oligonucleotide to noggin on the expression of nestin and GFAP in the hippocampus of adult rats%反义Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐海伟; 范晓棠

    2005-01-01

    目的探讨Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响.方法反义寡核苷酸技术封闭内源性Noggin基因的表达,免疫组化法检测成年大鼠海马内Nestin与GFAP的表达.结果侧脑室连续4 d注射Noggin基因的反义寡核苷酸后,可见海马齿状回(dentate gyrus,DG)内Nestin阳性细胞数与GFAP阳性细胞数较对照组显著增加;室下区GFAP阳性细胞数亦明显增加.结论Noggin对成年海马干细胞的分化有重要作用,内源性Noggin基因的表达可使神经干细胞向神经元方向分化.%Objective To examine the role of noggin on the expression of nestin and glial fibrillary acidic protein (GFAP) in the hippocampus of adult rats. Methods Antisense oligodeoxynucleotide (ASODN) technique was employed to inhibit endogenous noggin expression and immunohistochemistry was used to detect the expressions of Nestin and GFAP in the hippocampus of adult rats. Results It was observed that the number of nestin and GFAP immunoreactive cells in the dentate gyrus (DG) of hippocampus was increased in adult rats treated with antisense oligodeoxynucleotide to noggin. Moreover, the number of GFAP immunoreactive cells was increased in the subventricular zone of the rats treated with antisense oligodeoxynucleotide to noggin. Conclusion The results in the present study indicates that noggin may play a role in the differentiation of neural stem cells in the adult hippocampus, and it promotes the differentiation of neural stem cells in the DG to neuronal fate.

  6. GABA(A) Increases Calcium in Subventricular Zone Astrocyte-Like Cells Through L- and T-Type Voltage-Gated Calcium Channels

    DEFF Research Database (Denmark)

    Young, Stephanie Z; Platel, Jean-Claude; Nielsen, Jakob V;

    2010-01-01

    intracellular Ca(2+) dynamics in SVZ astrocytes. To monitor Ca(2+) activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP) promoter. GABA(A) receptor activation......-like cells to 75%, suggesting that the majority of SVZ astrocytes express functional VGCCs. SVZ astrocytes also displayed spontaneous Ca(2+) activity, the frequency of which was regulated by tonic GABA(A) receptor activation. These data support a role for ambient GABA in tonically regulating intracellular Ca...

  7. 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1- methylpyridine oxalate, a novel xanomeline derivative, improves neural cells proliferation and survival in adult mice

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang Zhang; Qiang Gong; Shuang Zhang; Lin Wang; Yinghe Hu; Haiming Shen; Suzhen Dong

    2012-01-01

    The present study analyzed the influence of 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1-methylpyridine oxalate (EUK1001), a novel xanomeline derivative of the M1/M4 receptor agonist, on hippocampal neurogenesis in adult C57BL6 mice. Results showed that 15-day EUK1001 treatment via intraperitoneal injection promoted neural cell proliferation in the dentate gyrus, although cell differentiation did not change. The majority of bromodeoxyuridine-positive cells co-expressed the immature neuronal marker doublecortin. In addition, the level of neurogenesis in the subventricular zone was not altered. Brain-derived neurotrophic factor mRNA expression was up-regulated following EUK1001 treatment, but no change was observed in expression of camp-responsive element binding protein 1, paired box gene 6, vascular endothelial growth factor alpha, neurogenic differentiation factor 1, and wingless-related mouse mammary tumor virus integration site 3A mRNA. These experimental findings indicated that EUK1001 enhanced proliferation and survival of hippocampal cells, possibly by increasing brain-derived neurotrophic factor expression.

  8. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

    Directory of Open Access Journals (Sweden)

    Shiva Mansouri

    Full Text Available Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP and the glucagon-like peptide-1 receptor (GLP-1R agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia.

  9. Distinct effects of chronic dopaminergic stimulation on hippocampal neurogenesis and striatal doublecortin expression in adult mice

    Directory of Open Access Journals (Sweden)

    Rachele eSalvi

    2016-03-01

    Full Text Available While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG and the subventricular zone (SVZ, recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g. the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX and Ropinirole (ROP, on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU a proliferation paradigm was performed in which two BrdU injections (100 mg/kg were applied intraperitoneally within 12 hours after a 14-day-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and NeuN 32 days after the last of five BrdU injections (50 mg/kg applied at the beginning of 14-day DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX+ neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active and

  10. Occurrence of new neurons in the piriform cortex

    OpenAIRE

    Ti-Fei eYuan; YU-XIANG eLIANG; Kwok-Fai eSo

    2015-01-01

    Adult neurogenesis has been well studied in hippocampus and subventricular zone; while this is much less appreciated in other brain regions, including amygdala, hypothalamus and piriform cortex. The present review aims at summarizing recent advances on the occurrence of new neurons in the piriform cortex, their potential origin and migration route from the subventricular zone. We further discuss the relevant implications in olfactory dysfunction accompanying the neuro-degenerative diseases.

  11. Occurrence of new neurons in the piriform cortex

    Directory of Open Access Journals (Sweden)

    Ti-Fei eYuan

    2015-01-01

    Full Text Available Adult neurogenesis has been well studied in hippocampus and subventricular zone; while this is much less appreciated in other brain regions, including amygdala, hypothalamus and piriform cortex. The present review aims at summarizing recent advances on the occurrence of new neurons in the piriform cortex, their potential origin and migration route from the subventricular zone. We further discuss the relevant implications in olfactory dysfunction accompanying the neuro-degenerative diseases.

  12. Germinal zones in the developing cerebral cortex of ferret: ontogeny, cell cycle kinetics, and diversity of progenitors.

    Science.gov (United States)

    Reillo, Isabel; Borrell, Víctor

    2012-09-01

    Expansion and folding of the cerebral cortex are landmark features of mammalian brain evolution. This is recapitulated during embryonic development, and specialized progenitor cell populations known as intermediate radial glia cells (IRGCs) are believed to play central roles. Because developmental mechanisms involved in cortical expansion and folding are likely conserved across phylogeny, it is crucial to identify features specific for gyrencephaly from those unique to primate brain development. Here, we studied multiple features of cortical development in ferret, a gyrencephalic carnivore, in comparison with primates. Analyzing the combinatorial expression of transcription factors, cytoskeletal proteins, and cell cycle parameters, we identified a combination of traits that distinguish in ferret similar germinal layers as in primates. Transcription factor analysis indicated that inner subventricular zone (ISVZ) and outer subventricular zone (OSVZ) may contain an identical mixture of progenitor cell subpopulations in ferret. However, we found that these layers emerge at different time points, differ in IRGC abundance, and progenitors have different cell cycle kinetics and self-renewal dynamics. Thus, ISVZ and OSVZ are likely distinguished by genetic differences regulating progenitor cell behavior and dynamics. Our findings demonstrate that some, but not all, features of primate cortical development are shared by the ferret, suggesting a conserved role in the evolutionary emergence of gyrencephaly.

  13. Adult neurogenesis in the mammalian brain: exogenous and endogenous influences%哺乳动物成体神经元的再生:内、外环境因子的作用

    Institute of Scientific and Technical Information of China (English)

    ChristieD.FOWLER; WANGZuo-Xin

    2003-01-01

    哺乳动物成体神经元的再生现象是最近三十年才被科学家们所认识并逐渐接受的.随着科研方法与实验技术的发展,在成年哺乳动物的一些特定脑区,比如海马齿状回(Dentate gyrus of the hippocampus)、室下区(Subventricular zone)和杏仁核(Amygdala)中发现了新生细胞.研究表明,内外环境因子可影响成体神经元的再生.具体表现在环境多样性、自主活动、有益社会交往、短日光照、化学刺激以及诸如5-羟色胺和脑源性神经营养因子等神经递质水平的增加,都会促进新生细胞的增生或存活.而负面社会交往及应激激素皮质酮对成体神经元的再生有抑制和降低作用.研究还表明,根据种和性别的差异,类脂醇激素对成体神经元的再生起到促进或抑制作用.最新的实验证实新生细胞在成体中具有显著功能%Until the past three decades, the general scientific community did not regard adult mammalian neurogenesis as an actual phenomenon. However, with the advent of new scientific methods and techniques, researchers have been able to identify and characterize new cells proliferating in several brain regions, including the dentate gyrus of the hippocampus, subventricular zone, and amygdala. Recently, studies have provided evidence that environmental factors, both external and internal, may influence adult neurogenesis. Specifically, the addition and/or survival of newly proliferated cells in various regions of the adult brain may be increased by environmental enrichment, voluntary activity, positive social interactions, short-day length, chemosensory stimuli, or increased levels of neurotransmitters including serotonin and brain-derived neurotrophic factor. Adult neurogenesis may be inhibited/decreased by negative social interactions or the stress hormone corticosterone. Interestingly, gonadal steroid hormones may exert positive or negative effects depending on the species and sex of the animal

  14. Neural precursors (NPCs) from adult L967Q mice display early commitment to "in vitro" neuronal differentiation and hyperexcitability.

    Science.gov (United States)

    DiFebo, Francesca; Curti, Daniela; Botti, Francesca; Biella, Gerardo; Bigini, Paolo; Mennini, Tiziana; Toselli, Mauro

    2012-08-01

    The pathogenic factors leading to selective degeneration of motoneurons in ALS are not yet understood. However, altered functionality of voltage-dependent Na(+) channels may play a role since cortical hyperexcitability was described in ALS patients and riluzole, the only drug approved to treat ALS, seems to decrease glutamate release via blockade or inactivation of voltage-dependent Na(+) channels. The wobbler mouse, a murine model of motoneuron degeneration, shares some of the clinical features of human ALS. At early stages of the wobbler disease, increased cortical hyperexcitability was observed. Moreover, riluzole reduced motoneuron loss and muscular atrophy in treated wobbler mice. Here, we focussed our attention on specific electrophysiological properties, like voltage-activated Na(+) currents and underlying regenerative electrical activity, as read-outs of the neuronal maturation process of neural stem/progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of adult early symptomatic wobbler mice. In self-renewal conditions, the rate of wobbler NPC proliferation "in vitro" was 30% lower than that of healthy mice. Conversely, the number of wobbler NPCs displaying early neuronal commitment and action potentials was significantly higher. Upon switching from proliferative to differentiative conditions, NPCs underwent significant changes in the key properties of voltage gated Na(+) currents. The most notable finding, in cells with neuronal morphology, was an increase in Na(+) current density that strictly correlated with an increased probability to generate action potentials. This feature was remarkably more pronounced in neurons differentiated from wobbler NPCs that upon sustained stimulation, displayed short trains of pathological facilitation. In agreement with this result, an increase in the number of c-Fos positive cells, a surrogate marker of neuronal network activation, was observed in the mesial cortex of the wobbler mice "in situ". Thus these

  15. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Song, Min; Wang, Yanyan [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Fan, Xiaotang [Department of Histology and Embryology, Third Military Medical University, Chongqing 400038 (China); Xu, Haiwei, E-mail: haiweixu2001@yahoo.com.cn [Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Bai, Yun, E-mail: baiyungene@gmail.com [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China)

    2009-07-31

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  16. Pharmacological blockade of either, cannabinoid CB1 or CB2 receptors, prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rats.

    Directory of Open Access Journals (Sweden)

    EDUARDO eBLANCO-CALVO

    2014-01-01

    Full Text Available Addiction to major drugs of abuse such as cocaine has been recently linked to alterations on adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulated this proliferative response since pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors by modulating not only neurogenesis but also cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation . To this end we examined if pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg or CB2 receptors (AM630, 3 mg/kg affects cell proliferation (labeled with BrdU, found in the subventricular zone (SVZ of the lateral ventricles and the dentate subgranular zone (SGZ. In addition, we measured cell apoptosis (monitored by the expression of cleaved caspase-3 and glial activation ( by analizing the expression of GFAP and Iba-1 in the striatum and hippocampus, during acute or repeated (4 days cocaine administration (20 mg/kg. Results showed that acute cocaine decreased the number of BrdU+ cells in SVZ and SGZ. In contrast, repeated cocaine reduced the number of BrdU+ cells in SVZ only. Both acute and repeated cocaine increased the number of cleaved caspase-3+, GFAP+ and Iba1+ cells in the hippocampus, an effect counteracted by AM630 or Rimonabant that increased the number of BrdU+, GFAP+ and Iba1+ cells in the hippocampus. These results indicate that changes on neurogenic, apoptotic and gliosis processes, which were produced as a consequence of repeated cocaine administration, were normalized by the pharmacological blockade of CB1 and CB2. The restoring effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with a prevention of the induction of conditioned locomotion, but not of cocaine-induced sensitization.

  17. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2'-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion

  18. Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer’s disease mice

    Institute of Scientific and Technical Information of China (English)

    Yufang Yan; Tuo Ma; Kai Gong; Qiang Ao; Xiufang Zhang; Yandao Gong

    2014-01-01

    In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer’s disease model mice. Immunofluorescence staining revealed that the number of newly generated (BrdU+) cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer’s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU+/DCX+neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer’s disease mice, thereby facilitating functional recovery.

  19. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

  20. The neuro-glial properties of adipose-derived adult stromal (ADAS cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Directory of Open Access Journals (Sweden)

    Philip C Wrage

    Full Text Available We investigated whether adipose-derived adult stromal (ADAS are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+ transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH; and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be

  1. Adult Neurogenesis in Fish.

    Science.gov (United States)

    Ganz, Julia; Brand, Michael

    2016-07-01

    Teleost fish have a remarkable neurogenic and regenerative capacity in the adult throughout the rostrocaudal axis of the brain. The distribution of proliferation zones shows a remarkable conservation, even in distantly related teleost species, suggesting a common teleost ground plan of proliferation zones. There are different progenitor populations in the neurogenic niches-progenitors positive for radial glial markers (dorsal telencephalon, hypothalamus) and progenitors with neuroepithelial-like characteristics (ventral telencephalon, optic tectum, cerebellum). Definition of these progenitors has allowed studying their role in normal growth of the adult brain, but also when challenged following a lesion. From these studies, important roles have emerged for intrinsic mechanisms and extrinsic signals controlling the activation of adult neurogenesis that enable regeneration of the adult brain to occur, opening up new perspectives on rekindling regeneration also in the context of the mammalian brain.

  2. Involvement of calpains in adult neurogenesis: implications for stroke

    Directory of Open Access Journals (Sweden)

    Vanessa Mendes Machado

    2015-02-01

    Full Text Available Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke models. On the other hand, after stroke, neural stem cells increase their proliferation and newly formed neuroblasts migrate towards the site of injury. However, the process of forming new neurons after injury is not efficient and finding ways to improve it may help with recovery after lesion. Understanding the role of calpains in the process of neurogenesis may therefore open a new window for the treatment of stroke. We investigated the involvement of calpains in neural stem cell proliferation and neuroblast migration in two highly neurogenic regions in the mouse brain, the dentate gyrus and the subventricular zone. We used mice that lack calpastatin, the endogenous calpain inhibitor, and calpains were also modulated directly, using calpeptin, a pharmacological calpain inhibitor. Calpastatin deletion impaired both neural stem cell proliferation and neuroblast migration. Calpain inhibition increased neural stem cell proliferation, migration speed and migration distance in cells from the subventricular zone. Overall, our work suggests that calpains are important for neurogenesis and warrant further research on how they influence the formation of new neurons. Prospective therapies targeting calpain activity not only may afford neuroprotection following stroke, but also benefit the formation and survival of new neurons.

  3. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    Institute of Scientific and Technical Information of China (English)

    Donnahue; Dennie; Jean-Pierre; Louboutin; David; S; Strayer

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors

  4. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    Science.gov (United States)

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  5. Zoning Districts, Zoning, Published in 2002, Freelance.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Zoning Districts dataset, was produced all or in part from Hardcopy Maps information as of 2002. It is described as 'Zoning'. Data by this publisher are often...

  6. Testosterone-induced adult neurosphere growth is mediated by sexually-dimorphic aromatase expression

    Directory of Open Access Journals (Sweden)

    Mark Ian Ransome

    2015-07-01

    Full Text Available We derived adult neural stem/progenitor cells (NSPCs from the sub-ventricular zone of male and female mice to examine direct responses to principal sex hormones. In the presence of epidermal growth factor (EGF and fibroblast growth factor-2 (FGF2 NSPCs of both sexes expressed nestin and sox2 and could be maintained as neurospheres without addition of any sex hormones. The reverse was not observed; neither testosterone (T, 17β-oestradiol (E2 nor progesterone (P4 was able to support neurosphere growth in the absence of EGF and FGF2. 10nM T, E2 or P4 induced nestin(+ cell proliferation within 20 minutes and enhanced neurosphere growth over 7 days irrespective of sex, which was abolished by Erk inhibition with 20M U0126. Maintaining neurospheres with each sex hormone did not affect subsequent neuronal differentiation. However, 10nM T, E2 or P4 added during differentiation increased III tubulin(+ neuron production with E2 being more potent compared to T and P4 in both sexes. Androgen receptor (AR inhibition with 20M flutamide but not aromatase inhibition with 10M letrozole reduced basal and T-induced neurosphere growth in females, while only concurrent inhibition of AR and aromatase produced the same effect in males. This sex-specific effect was supported by higher aromatase expression in male neurospheres compared to females measured by Western blot and green fluorescent protein reporter. 10M menadione induced oxidative stress, impaired neurosphere growth and up-regulated aromatase expression in both sexes. However, under oxidative stress letrozole significantly exacerbated impaired neurosphere growth in males only. While both E2 and T could prevent oxidative stress-induced growth reduction in both sexes, the effects of T were dependent on innate aromatase activity. We show for the first time that intrinsic androgen and estrogen signalling may impact the capacity of NSPCs to produce neural progenitors under pathological conditions of

  7. Adult neurogenesis in the hedgehog (Erinaceus concolor) and mole (Talpa europaea).

    Science.gov (United States)

    Bartkowska, K; Turlejski, K; Grabiec, M; Ghazaryan, A; Yavruoyan, E; Djavadian, R L

    2010-01-01

    We investigated adult neurogenesis in two species of mammals belonging to the superorder Laurasiatheria, the southern white-breasted hedgehog (order Erinaceomorpha, species Erinaceus concolor) from Armenia and the European mole (order Soricomorpha, species Talpa europaea) from Poland. Neurogenesis in the brain of these species was examined immunohistochemically, using the endogenous markers doublecortin (DCX) and Ki-67, which are highly conserved among species. We found that in both the hedgehog and mole, like in the majority of earlier investigated mammals, neurogenesis continues in the subventricular zone (SVZ) of the lateral ventricles and in the dentate gyrus (DG). In the DG of both species, DCX-expressing cells and Ki-67-labeled cells were present in the subgranular and granular layers. In the mole, a strong bundle of DCX-labeled processes, presumably axons of granule cells, was observed in the center of the hilus. Proliferating cells (expressing Ki-67) were identified in the SVZ of lateral ventricles of both species, but neuronal precursor cells (expressing DCX) were also observed in the olfactory bulb (OB). In both species, the vast majority of cells expressing DCX in the OB were granule cells with radially orientated dendrites, although some periglomerular cells surrounding the glomeruli were also labeled. In addition, this paper is the first to show DCX-labeled fibers in the anterior commissure of the hedgehog and mole. These fibers must be axons of new neurons making interhemispheric connections between the two OB or piriform (olfactory) cortices. DCX-expressing neurons were observed in the striatum and piriform cortex of both hedgehog and mole. We postulate that in both species a fraction of cells newly generated in the SVZ migrates along the rostral migratory stream to the piriform cortex. This pattern of migration resembles that of the 'second-wave neurons' generated during embryonal development of the neocortex rather than the pattern observed during

  8. New neurons in aging brains: molecular control by small non-coding RNAs.

    NARCIS (Netherlands)

    M. Schouten; M.R. Buijink; P.J. Lucassen; C.P. Fitzsimons

    2012-01-01

    Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of th

  9. Biciliated ependymal cell proliferation contributes to spinal cord growth

    OpenAIRE

    Alfaro-Cervello, Clara; Soriano-Navarro, Mario; Mirzadeh, Zaman; Alvarez-Buylla, Arturo; García Verdugo, José Manuel

    2012-01-01

    Two neurogenic regions have been described in the adult brain, the lateral ventricle subventricular zone and the dentate gyrus subgranular zone. It has been suggested that neural stem cells also line the central canal of the adult spinal cord. Using transmission and scanning electron microscopy and immunostaining, we describe here the organization and cell types of the central canal epithelium in adult mice. The identity of dividing cells was determined by three-dimensional ultrastructural re...

  10. The role of adult neurogenesis in psychiatric and cognitive disorders.

    Science.gov (United States)

    Apple, Deana M; Fonseca, Rene Solano; Kokovay, Erzsebet

    2017-01-15

    Neurogenesis in mammals occurs throughout life in two brain regions: the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Development and regulation of the V-SVZ and SGZ is unique to each brain region, but with several similar characteristics. Alterations to the production of new neurons in neurogenic regions have been linked to psychiatric and neurodegenerative disorders. Decline in neurogenesis in the SGZ correlates with affective and psychiatric disorders, and can be reversed by antidepressant and antipsychotic drugs. Likewise, neurogenesis in the V-SVZ can also be enhanced by antidepressant drugs. The regulation of neurogenesis by neurotransmitters, particularly monoamines, in both regions suggests that aberrant neurotransmitter signaling observed in psychiatric disease may play a role in the pathology of these mental health disorders. Similarly, the cognitive deficits that accompany neurodegenerative disease may also be exacerbated by decreased neurogenesis. This review explores the regulation and function of neural stem cells in rodents and humans, and the involvement of factors that contribute to psychiatric and cognitive deficits. This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry.

  11. Adult Strabismus

    Science.gov (United States)

    ... cause. Is eye straightening as an adult strictly cosmetic? No. Eye alignment surgery is performed in adults for several reasons. Adults ... this surgery? Eye muscle surgery is reconstructive (not cosmetic). In ... will cover strabismus surgery in adults, however, one should check with their ...

  12. Novel primate miRNAs coevolved with ancient target genes in germinal zone-specific expression patterns.

    Science.gov (United States)

    Arcila, Mary L; Betizeau, Marion; Cambronne, Xiaolu A; Guzman, Elmer; Doerflinger, Nathalie; Bouhallier, Frantz; Zhou, Hongjun; Wu, Bian; Rani, Neha; Bassett, Danielle S; Borello, Ugo; Huissoud, Cyril; Goodman, Richard H; Dehay, Colette; Kosik, Kenneth S

    2014-03-19

    Major nonprimate-primate differences in cortico-genesis include the dimensions, precursor lineages, and developmental timing of the germinal zones (GZs). microRNAs (miRNAs) of laser-dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including ventricular zone (VZ) and outer and inner subcompartments of the outer subventricular zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but absent in rodent, contributed disproportionately to the differential expression between GZ subregions. Prominent among the validated targets of these miRNAs were cell-cycle and neurogenesis regulators. Coevolution between the emergent miRNAs and their targets suggested that novel miRNAs became integrated into ancient gene circuitry to exert additional control over proliferation. We conclude that multiple cell-cycle regulatory events contribute to the emergence of primate-specific cortical features, including the OSVZ, generated enlarged supragranular layers, largely responsible for the increased primate cortex computational abilities.

  13. ZoneLib

    DEFF Research Database (Denmark)

    Jessen, Jan Jacob; Schiøler, Henrik

    2006-01-01

    We present a dynamic model for climate in a livestock building divided into a number of zones, and a corresponding modular Simulink library (ZoneLib). While most literature in this area consider air flow as a control parameter we show how to model climate dynamics using actual control signals...... development of ZoneLib....

  14. Generalized Fibonacci zone plates

    CERN Document Server

    Ke, Jie; Zhu, Jianqiang

    2015-01-01

    We propose a family of zone plates which are produced by the generalized Fibonacci sequences and their axial focusing properties are analyzed in detail. Compared with traditional Fresnel zone plates, the generalized Fibonacci zone plates present two axial foci with equal intensity. Besides, we propose an approach to adjust the axial locations of the two foci by means of different optical path difference, and further give the deterministic ratio of the two focal distances which attributes to their own generalized Fibonacci sequences. The generalized Fibonacci zone plates may allow for new applications in micro and nanophotonics.

  15. Shanghai's Development Zones

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Since the early 1980s,development zones began appearing in China.Their Success largely stems from the preferential policies they offer and the safe investment environment they work hard to create.As zones have personalities themselves,it is essential to look beyond the pamphlets and published information and get down to the nittygritty.Shanghai has more State designated Economic and Technology Development Zones than any other city in China.In the following article,we have chosen development zones located around Shanghai and conducted a comparison.

  16. Adult Education and Adult Learning

    DEFF Research Database (Denmark)

    Illeris, Knud

    Kort beskrivelse Bogen, 'Adult Education og Adult Learning', giver et fyldestgørende overblik over forståelsen af voksenuddannelse og læring. Abstract I "Adult Education and Adult Learning' ser Knud Illeris på voksenuddannelse fra to perspektiver. På den ene side beskrives de aktuelle udfordringer...

  17. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  18. Role of BMP2 in differentiation of neural stem cells from anterior subventricular zone into GABAergic neurons%BMP2在SVZa神经干细胞向GABA能神经元分化中的调控作用

    Institute of Scientific and Technical Information of China (English)

    陈锦华; 杨辉; 尹昌林; 张治元; 刘仕勇; 何家全; 高方友

    2007-01-01

    目的 研究BMP2在SVZa神经干细胞向γ-氨基丁酸(GABA)能神经元分化中的调控作用.方法 体外分离培养P0昆明小鼠室管膜下区(SVZa)神经干细胞,纯化传代培养3代后,使用不同浓度BMP2诱导SVZa神经干细胞,采用流式细胞仪检测不同浓度BMP2作用下SVZa神经干细胞分化为GABA能神经元的比例;另外利用活体荧光GFP标记GAD67特异性启动子,动态地研究BMP2在SVZa神经干细胞向GABA能神经元分化中的作用.在此基础之上,采用RT-PCR检测不同浓度BMP2作用下Mash1的表达.结果 不同浓度BMP2作用组分化为GABA能神经元的比例均高于空白对照组,10 ng/ml浓度的BMP2组比例最高;10 ng/ml浓度BMP2组,GAD67-GFP标记阳性细胞数目明显高于对照组;10 ng/ml浓度BMP2组Mash1表达高于其他组.结论 BMP2促进SVZa神经干细胞向GABA能神经元的分化;10 ng/ml浓度的BMP2显著促进Mash1的表达.

  19. Subduction of fracture zones

    Science.gov (United States)

    Constantin Manea, Vlad; Gerya, Taras; Manea, Marina; Zhu, Guizhi; Leeman, William

    2013-04-01

    Since Wilson proposed in 1965 the existence of a new class of faults on the ocean floor, namely transform faults, the geodynamic effects and importance of fracture zone subduction is still little studied. It is known that oceanic plates are characterized by numerous fracture zones, and some of them have the potential to transport into subduction zones large volumes of water-rich serpentinite, providing a fertile water source for magma generated in subduction-related arc volcanoes. In most previous geodynamic studies, subducting plates are considered to be homogeneous, and there is no clear indication how the subduction of a fracture zone influences the melting pattern in the mantle wedge and the slab-derived fluids distribution in the subarc mantle. Here we show that subduction of serpentinized fracture zones plays a significant role in distribution of melt and fluids in the mantle wedge above the slab. Using high-resolution tree-dimensional coupled petrological-termomechanical simulations of subduction, we show that fluids, including melts and water, vary dramatically in the region where a serpentinized fracture zone enters into subduction. Our models show that substantial hydration and partial melting tend to concentrate where fracture zones are being subducted, creating favorable conditions for partially molten hydrous plumes to develop. These results are consistent with the along-arc variability in magma source compositions and processes in several regions, as the Aleutian Arc, the Cascades, the Southern Mexican Volcanic Arc, and the Andean Southern Volcanic Zone.

  20. Polymyositis - adult

    Science.gov (United States)

    ... rash is a sign of a similar condition, dermatomyositis . Common symptoms include: Muscle weakness in the shoulders ... in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. ...

  1. The Regenerative Response of Endogenous Neural Stem/Progenitor Cells to Traumatic Brain Injury

    Science.gov (United States)

    2014-06-09

    neural stem cells in the adjacent SVZ, the largest germinal zone in the mammalian CNS. Ex vivo and in vivo DTI were combined with post-imaging...faults accrued over 50 steps was counted for each hind limb. Controlled Cortical Impact (CCI), which involves craniotomy and impact onto the dura...the subventricular zone (SVZ), a major germinal zone in the adult brain, have potential repair capacity that is not well understood relative to the

  2. Microgravity silicon zoning investigation

    Science.gov (United States)

    Kern, E. L.; Gill, G. L., Jr.

    1985-01-01

    The flow instabilities in floating zones of silicon were investigated and methods for investigation of these instabilities in microgravity were defined. Three principal tasks were involved: (1) characterization of the float zone in small diameter rods; (2) investigation of melt flow instabilities in circular melts in silicon disks; and (3) the development of a prototype of an apparatus that could be used in near term space experiments to investigate flow instabilities in a molten zone. It is shown that in a resistance heated zoner with 4 to 7 mm diameter silicon rods that the critical Marangoni number is about 1480 compared to a predicted value of 14 indicative that viable space experiments might be performed. The prototype float zone apparatus is built and specifications are prepared for a flight zoner should a decision be reached to proceed with a space flight experimental investigation.

  3. The gray zone.

    Science.gov (United States)

    Kisner, H J

    1998-01-01

    Think for a minute about the terms equivocal and indeterminate. Equivocal is defined as "of uncertain significance", and indeterminate is defined as "indefinite, uncertain". Now think of the context in which laboratory results are reported: either by using the exact words equivocal or indeterminate or cloaked in technical jargon (e.g., cytologic diagnoses "ASCUS" or "AGUS"). Clinicians expect (or at least want) laboratory results to be black or white (i.e., bimodally distributed), whereas laboratorians strive for the perfect shade of gray because of data that often are bimodal but overlapping. A consequence of this color war is "the gray zone" (often confused with the "twilight zone"), a noncommittal zone that leaves laboratorians and clinicians alike plenty of wiggle room, allowing us to interpret results on either side of the fence. This article examines the root causes of the gray zone, with several clinical examples of how it permeates laboratory interpretation.

  4. Promise Zones for Applicants

    Data.gov (United States)

    Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...

  5. BLM Solar Energy Zones

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — Priority development areas for utility-scale solar energy facilities as identified in the Solar PEIS Record of Decision. An additional Solar Energy Zone identified...

  6. Simulated floating zone method

    OpenAIRE

    Ozawa, Ryo; Kato, Yasuyuki; Motome, Yukitoshi

    2016-01-01

    This paper provides the simulated floating zone (SFZ) method that is an efficient simulation technique to obtain thermal equilibrium states, especially useful when domain formation prevents the system from reaching a spatially-uniform stable state. In the SFZ method, the system is heated up locally, and the heated region is steadily shifted, similar to the floating zone method for growing a single crystal with less lattice defect and impurity in experiments. We demonstrate that the SFZ method...

  7. Involvement of calpains in adult neurogenesis: implications for stroke.

    Science.gov (United States)

    Machado, Vanessa M; Morte, Maria I; Carreira, Bruno P; Azevedo, Maria M; Takano, Jiro; Iwata, Nobuhisa; Saido, Takaomi C; Asmussen, Hannelore; Horwitz, Alan R; Carvalho, Caetana M; Araújo, Inês M

    2015-01-01

    Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke models. On the other hand, after stroke, neural stem cells (NSC) increase their proliferation and newly formed neuroblasts migrate towards the site of injury. However, the process of forming new neurons after injury is not efficient and finding ways to improve it may help with recovery after lesion. Understanding the role of calpains in the process of neurogenesis may therefore open a new window for the treatment of stroke. We investigated the involvement of calpains in NSC proliferation and neuroblast migration in two highly neurogenic regions in the mouse brain, the dentate gyrus (DG) and the subventricular zone (SVZ). We used mice that lack calpastatin, the endogenous calpain inhibitor, and calpains were also modulated directly, using calpeptin, a pharmacological calpain inhibitor. Calpastatin deletion impaired both NSC proliferation and neuroblast migration. Calpain inhibition increased NSC proliferation, migration speed and migration distance in cells from the SVZ. Overall, our work suggests that calpains are important for neurogenesis and encourages further research on their neurogenic role. Prospective therapies targeting calpain activity may improve the formation of new neurons following stroke, in addition to affording neuroprotection.

  8. Zones of emotional labour

    DEFF Research Database (Denmark)

    Strøbæk, Pernille Solveig

    2011-01-01

    is put forth among 25 Danish public family law caseworkers. The study points to personal, professional, and social zones of emotional labour through which the caseworkers carry out their work. Emotional labour zones mark emotion structures that may be challenging due to complex emotional intersections......The paper suggests that due to the difficult nature of their work public family law caseworkers are to be included in the definition of emotional labour even though they are omitted by Hochschild. Based upon a review of the structures involved in emotional labour an explorative qualitative study...

  9. Panic Disorder among Adults

    Science.gov (United States)

    ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ...

  10. Major Depression Among Adults

    Science.gov (United States)

    ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ...

  11. Flexible 'zoning' aids adaptability.

    Science.gov (United States)

    Corben, Simon

    2013-09-01

    Simon Corben, business development director at Capita Symonds' Health team, examines how 'clever use of zoning' when planning new healthcare facilities could improve hospital design, increase inherent flexibility, and reduce lifetime costs, and argues that a 'loose-fit, non-bespoke approach' to space planning will lead to 'more flexible buildings that are suitable for conversion to alternative uses'.

  12. DNS zones revisited

    NARCIS (Netherlands)

    Wanrooij, van Ward; Pras, Aiko; Delgado Kloos, Carlos

    2005-01-01

    Recent research [Pap04b] suggests DNS reliability and performance is not up to the levels it should be due to misconfigurations. This paper checks the configuration of nameserver zones against additional requirements, recommendations and best-practices. It shows that almost one in four domains fails

  13. Transport of larvae and detritus across the surf zone of a steep reflective pocket beach

    NARCIS (Netherlands)

    Shanks, A.L.; MacMahan, J.; Morgan, S.G.; Reniers, A.J.H.M.; Jarvis, M.; Brown, J.; Fujimura, A.; Griesemer, C.

    2015-01-01

    Larvae of many intertidal species develop offshore and must cross the surf zone to complete their onshore migration to adult habitats. Depending on hydrodynamics, the surf zone may limit this migration, especially on reflective rocky shores. As a logistically tractable analog of a rocky shore enviro

  14. Adult teachers

    DEFF Research Database (Denmark)

    Larsen, Lea Lund

    2011-01-01

    In this paper I examine the research into the process of adult teachers’ practice-based learning as a part of an on-going project titled “Competence development through practice-based learning – a study of adult teacher’s learning processes”. The project relies on the notion of the adult teacher...... as a 'reflective practitioner’, who develops 'the language of practice’, through experience and learns when she is exposed to 'disjuncture’. Research done on continuing professional development and the inquiries done in the field of teacher thinking and within this the research on novices becoming expert...

  15. Empowerment Zones and Enterprise Districts - MDC_EnterpriseZone

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — Polygon feature class of Miami Dade County Enterprise Zones. Enterprise Zones are special areas in the county where certain incentives from the State are available...

  16. The Habitable Zone Gallery

    CERN Document Server

    Kane, Stephen R

    2012-01-01

    The Habitable Zone Gallery (www.hzgallery.org) is a new service to the exoplanet community which provides Habitable Zone (HZ) information for each of the exoplanetary systems with known planetary orbital parameters. The service includes a sortable table with information on the percentage of orbital phase spent within the HZ, planetary effective temperatures, and other basic planetary properties. In addition to the table, we also plot the period and eccentricity of the planets with respect to their time spent in the HZ. The service includes a gallery of known systems which plot the orbits and the location of the HZ with respect to those orbits. Also provided are animations which aid in orbit visualization and provide the changing effective temperature for those planets in eccentric orbits. Here we describe the science motivation, the under-lying calculations, and the structure of the web site.

  17. Electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination.

    Science.gov (United States)

    Sherafat, Mohammad Amin; Heibatollahi, Motahareh; Mongabadi, Somayeh; Moradi, Fatemeh; Javan, Mohammad; Ahmadiani, Abolhassan

    2012-09-01

    Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within the brain. The aim of this study was to assess the effects of EMFs on the process of toxin-induced demyelination and subsequent remyelination. Demyelination was induced using local injection of lysophosphatidylcholine within the corpus callosum of adult female Sprague-Dawley rats. EMFs (60 Hz; 0.7 mT) were applied for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for assessing the amount of neural stem cells within the tissue, remyelination patterns, and tracing of proliferating cells, respectively. EMFs significantly reduced the extent of demyelinated area and increased the level of MBP staining within the lesion area on days 14 and 28 postlesion. EMFs also increased the number of BrdU- and nestin-positive cells within the area between SVZ and lesion as observed on days 7 and 14 postlesion. It seems that EMF potentiates proliferation and migration of neural stem cells and enhances the repair of myelin in the context of demyelinating conditions.

  18. ZONE OF COOPERATION

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The China-ASEAN Economic Zone is attracting more and more investors from both Southeast Asia and China Compared with other countries that have established free trade areas with ASEAN, China owns millions of unique advantages. Millions, after all, is the quantity of Chinese living in ASEAN countries. "With ties of blood, geography and commerce, business people of Chinese descent can be the best candidates to pro-

  19. Ecological zones of California deserts

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The dataset delineates ecological zones within California deserts. We derived ecological zones by reclassifying LANDFIRE vegetation biophysical setting types, plus...

  20. Radiant zone heated particulate filter

    Science.gov (United States)

    Gonze, Eugene V [Pinckney, MI

    2011-12-27

    A system includes a particulate matter (PM) filter including an upstream end for receiving exhaust gas and a downstream end. A radiant zoned heater includes N zones, where N is an integer greater than one, wherein each of the N zones includes M sub-zones, where M is an integer greater than or equal to one. A control module selectively activates at least a selected one of the N zones to initiate regeneration in downstream portions of the PM filter from the one of the N zones, restricts exhaust gas flow in a portion of the PM filter that corresponds to the selected one of the N zones, and deactivates non-selected ones of the N zones.

  1. The uncomfortable comfort zone

    Directory of Open Access Journals (Sweden)

    Carlos Renato Zacharias

    2012-04-01

    Full Text Available Whenever we achieve the satisfaction of our expectations and anxiety dissolves, we feel as if we were in a comfort zone – safe, complete, free from risks and in peace with ourselves. We might even have a little taste of heaven when we feel that we have fulfilled our duty. And as a fact, scientists are entitled to this kind of reward… but not for too long! In science, to enter a comfort zone can be as pleasant as dangerous. On one hand we may have a safe ground available to develop new modes of reasoning, protocols and theories. And on the other, we may stay stuck in a conventional but fragile ground, missing opportunities to reveal novel secrets or to address edge issues. ... The community of HD researchers seems to have entered a new comfort zone when nanostructures were found in HD. Nanostructures have been raised to the level of ultimate evidence doing away with Avogadro’s limit and leading homeopathy and HD research into mainstream science. We really should enjoy this moment and collect more information about the HD phenomenon. However, we must be wary to not fall into a trap.

  2. High hopes for CB2 receptors in neurogenesis

    OpenAIRE

    Downer, Eric J

    2014-01-01

    During life, new neurons are continually added to hippocampal circuitry, with evidence suggesting that these adult-born neurons are functionally linked to cognition and emotion. The mammalian brain contains actively dividing neural stem cells in discrete regions, including the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus. Once mature, these neurons integrate into neuronal networks, forming synaptic connections with interneurons, mossy cells and C...

  3. Smartphones and Time Zones

    Science.gov (United States)

    Baird, William; Secrest, Jeffery; Padgett, Clifford; Johnson, Wayne; Hagrelius, Claire

    2016-09-01

    Using the Sun to tell time is an ancient idea, but we can take advantage of modern technology to bring it into the 21st century for students in astronomy, physics, or physical science classes. We have employed smartphones, Google Earth, and 3D printing to find the moment of local noon at two widely separated locations. By reviewing GPS time-stamped photos from each place, we are able to illustrate that local noon is longitude-dependent and therefore explain the need for time zones.

  4. Parapapillary atrophy: histological gamma zone and delta zone.

    Directory of Open Access Journals (Sweden)

    Jost B Jonas

    Full Text Available BACKGROUND: To examine histomorphometrically the parapapillary region in human eyes. METHODOLOGY/PRINCIPAL FINDINGS: The histomorphometric study included 65 human globes (axial length:21-37 mm. On anterior-posterior histological sections, we measured the distance Bruch's membrane end (BME-optic nerve margin ("Gamma zone", BME-retinal pigment epithelium (RPE ("Beta zone", BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. "Delta zone" was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm was significantly (P = 0.01 larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28 associated with axial length. Beta zone was significantly (P = 0.004 larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm was associated with axial length (P50 µm diameter within gamma zone was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch's membrane without RPE was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.

  5. Does developmental hypothyroidism produce lasting effects on adult neurogenesis?

    Science.gov (United States)

    The subgranular zone of the dentate gyrus (DO) of the adult hippocampus generates new neurons throughout life. Thyroid hormones (TH) are essential for brain development, but impaired neurogenesis with adult hypothyroidism has also been reported. We investigated the role of milder...

  6. 成体神经干(前体)细胞在中枢神经系统退行性病变中的修复作用%Adult neural stem/progenitor cells in neurodegenerative repair

    Institute of Scientific and Technical Information of China (English)

    毛利民; 王强

    2003-01-01

    Although the mammalian brain has long been thought to be entirely postmitotic, the recent discovery has confirmed an existence of neural stem or progenitor cells in various regions of the adult mammalian brain. Like embryonic stem cells, adult neural progenitor cells possess the capacity of self-renewal and differentiation potential for neurogenesis or gliogenesis. In addition to the subventricular zone and hippocampus where active cell division naturally occurs, adult neural progenitors with neurogenic potential exist in the striatum and the vicinity of dopaminergic neurons in the substantia nigra. Normally, progenitors in those regions proliferate at a low level, and most proliferated cells remain uncommitted. In response to the selective lesion of nigrostriatal dopaminergic pathway by the neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine, progenitors in the injured areas markedly increase their proliferation rate. Depending upon the magnitude and kinetics of the lesion, neurogenesis and gliogenesis were induced in the lesion sites at varying extents. A large number of growth and neurotrophic factors influence proliferation and/or differentiation of progenitor cells under normal and lesioned conditions. Some factors (epidermal and basic fibroblast growth factors and brain-derived neurotrophic factor) are facilitatory, while others (usually bone morphogenetic proteins) are inhibitory, for controlling division and fate of neuronal or glial progenitors. Expression of endogenous factors and their respective receptors in existing and newborn cells are also subject to be altered by the lesion. These genomic responses are considered to be important elements for the formation of a local molecular niche for a given phenotypic cell regeneration. Taken together, adult neural progenitor cells in the nigrostriatal dopaminergic system have the ability to respond to the lesion to repopulate missing cells. The regenerative neuro- or

  7. Genetic Profiling to Determine Potential Origins of Boll Weevils (Coleoptera: Curculionidae) Captured in a Texas Eradication Zone: Endemicity, Immigration, or Sabotage

    Science.gov (United States)

    Five specimens of adult boll weevil, Anthonomus grandis, were captured nearly simultaneously in pheromone traps clustered near Lubbock, TX, in the Southern High Plains/Caprock eradication zone in late summer 2006. No boll weevils had been captured in this zone or neighboring zones to the north earl...

  8. The Near Zone to Far Zone Transformation (N2F)

    Energy Technology Data Exchange (ETDEWEB)

    Blackfield, Donald T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Poole, Brian R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-03-11

    N2F is a C/C++ code used to calculate the far zone electromagnetic (EM) field, given E and H near zone field data. The method used by N2F can be found in Ref. 1 and 2. N2F determines the far field EΦ and Eθ in spherical coordinates for near zone data calculated in either Cartesian or Cylindrical geometry.

  9. Empowerment Zones and Enterprise Districts - Volusia County Enterprise Zones

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — Florida's Enterprise Zone Program encourages economic growth and investment in distressed areas by offering tax advantages and incentives to businesses that are...

  10. Saturated Zone Colloid Transport

    Energy Technology Data Exchange (ETDEWEB)

    H. S. Viswanathan

    2004-10-07

    This scientific analysis provides retardation factors for colloids transporting in the saturated zone (SZ) and the unsaturated zone (UZ). These retardation factors represent the reversible chemical and physical filtration of colloids in the SZ. The value of the colloid retardation factor, R{sub col} is dependent on several factors, such as colloid size, colloid type, and geochemical conditions (e.g., pH, Eh, and ionic strength). These factors are folded into the distributions of R{sub col} that have been developed from field and experimental data collected under varying geochemical conditions with different colloid types and sizes. Attachment rate constants, k{sub att}, and detachment rate constants, k{sub det}, of colloids to the fracture surface have been measured for the fractured volcanics, and separate R{sub col} uncertainty distributions have been developed for attachment and detachment to clastic material and mineral grains in the alluvium. Radionuclides such as plutonium and americium sorb mostly (90 to 99 percent) irreversibly to colloids (BSC 2004 [DIRS 170025], Section 6.3.3.2). The colloid retardation factors developed in this analysis are needed to simulate the transport of radionuclides that are irreversibly sorbed onto colloids; this transport is discussed in the model report ''Site-Scale Saturated Zone Transport'' (BSC 2004 [DIRS 170036]). Although it is not exclusive to any particular radionuclide release scenario, this scientific analysis especially addresses those scenarios pertaining to evidence from waste-degradation experiments, which indicate that plutonium and americium may be irreversibly attached to colloids for the time scales of interest. A section of this report will also discuss the validity of using microspheres as analogs to colloids in some of the lab and field experiments used to obtain the colloid retardation factors. In addition, a small fraction of colloids travels with the groundwater without any significant

  11. Learning About Intervention Target Zones

    OpenAIRE

    Klein, Michael W; Karen K. Lewis

    1991-01-01

    This paper provides a framework for evaluating how market participants' beliefs about foreign exchange target zones change as they learn about central bank intervention policy. In order to examine this behavior, we first generalize the standard target zone model to allow for intra-marginal intervention. Intra-marginal intervention implies that the position of market participants' beliefs about the target zone can be determined from their beliefs about the likelihood of intervention. As an app...

  12. Zoning should promote public health.

    Science.gov (United States)

    Hirschhorn, Joel S

    2004-01-01

    Legally, governments use their police powers to protect public health, safety, and welfare through zoning. This paper presents a case for revisiting zoning on the basis of increasing evidence that certain types of community design promote public health, as opposed to the dominant pattern of sprawl development, which does not. Zoning, and the land use planning linked to it, that prohibits or disfavors health-promoting community designs contradicts the inherent public policy goal on which it is based. If there is a paradigm shift underway, from traditional sprawl to health-promoting community designs, then health professionals and others should understand why zoning must be reassessed.

  13. Work Zone Data Collection Trailer

    Data.gov (United States)

    Federal Laboratory Consortium — The Work Zone Data Collection Trailer was designed and constructed to enhance data collection and analysis capabilities for the "Evaluating Roadway Construction Work...

  14. Obstructive sleep apnea - adults

    Science.gov (United States)

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  15. Excavation damaged zone

    Energy Technology Data Exchange (ETDEWEB)

    Poulain, S.; Sergeant, C.; Vesvres, M.H.; Simonoff, M.; Lavielle, B.; Thomas, B.; Gilabert, E. [Bordeaux-1 Univ., I and 2/CNRS and GdR FORPRO 0788, Nuclear Analytical and Bioenvironmental Chemistry 33 - Gradignan (France); Poulain, S.; Altmann, S.; Lenoir, N.; Barnichon, J.D.; Wileveau, Y.; Lebon, P. [ANDRA - Agence Nationale pour la Gestion des Dechets Radioactifs, 92 - Chatenay Malabry (France); Le Marrec, C. [Bordeaux-1 Univ., ISTAB, INRA, UMR Oenologie - ISVV, 33 - Talence (France); Vinsot, A.; Dewonck, S.; Wileveau, Y.; Armand, G.; Cruchaudet, P.; Rebours, H.; Morel, J. [Agence Nationale pour la Gestion des Dechets Radioactifs, Lab. de Souterrain de Meuse/Haute-Marne, 55 - Bure (France); Lanyon, G.W. [Fracture Systems Ltd, Tregurrian, Ayr, St Ives, Cornwall (United Kingdom); Marschall, P.; Vietor, T. [NAGRA - National Cooperative for the Disposal of Radioactive Waste, Wettingen (Switzerland); Bourdeau, C.; Dedecker, F.; Billaux, D. [ITASCA Consultants, S.A.S., 69 - Ecully (France); Lenoir, N.; Desrues, J.; Viggiani, G.; Besuelle, P. [Laboratoire 3S-R - Sols Solides Structures-Risques, 38 - Grenoble (France); Bornert, M. [Ecole Polytechnique, LMS - Lab. de Mecanique des Solides, 91 - Palaiseau (France); Arson, C.; Gatmiri, B. [CERMES, Ecole Nationale des Ponts et Chaussees, 77 - Marne-la-Vallee (France); Gatmiri, B. [University of Tehran (Iran, Islamic Republic of); Bernier, F. [ESV EURIDICE GIE - European Underground Research Infrastructure for Disposal of Nuclear Waste in Clay Environment (Belgium); Nussbaum, C.; Mori, O. [Geotechnical Institute Ltd., Fabrique de Chaux, St-Ursanne (Switzerland); Bossart, P. [Swisstopo - Federal Office of Topography, Wabern (Switzerland); Schuster, K.; Alheid, H.J. [BGR - Bundesanstalt fur Geowissenschaften und Rohstoffe, Hannover (Germany); Lavanchy, J.M.; Croise, J.; Schwarz, R. [Colenco Power Engineering AG, Groundwater Protection and Waste Disposal, Baden (Switzerland)] [and others

    2007-07-01

    This session gathers 13 articles dealing with: autochthonous and colonizing microorganisms in argillaceous underground environments (S. Poulain, C. Sergeant, C. Le Marrec, M.H. Vesvres, A. Vinsot, S. Dewonck, M. Simonoff, S. Altmann); the discrete fracture network modelling of the Hg-a experiment at the Mont Terri rock Laboratory (G.W. Lanyon, P. Marschall, T. Vietor); the discrete modelling of drift behaviour in the Meuse/Haute-Marne URL, France (C. Bourdeau, F. Dedecker, D. Billaux); the fracturing in Callovo-Oxfordian argillite under triaxial compression studied by X-ray microtomography (N. Lenoir, J. Desrues, G. Viggiani, P. Besuelle, M. Bornert, J.D. Barnichon); a general review of the damage models for the EDZ creation (C. Arson, B. Gatmiri); similarities in the Hydro-Mechanical response of Callovo-Oxfordian clay and Boom clay during gallery excavation (Y. Wileveau, F. Bernier); the different geometries of the EDZ fracture networks in the Mont Terri and Meuse/Haute-Marne rock laboratories: Structural approach (C. Nussbaum, Y. Wileveau, P. Bossart, A. Moeri, G. Armand); the characterisation of the Excavation-Damaged Zone in the Meuse/Haute-Marne Underground Research Laboratory (G. Armand, P. Lebon, M. Cruchaudet, H. Rebours, J. Morel, Y. Wileveau); the EDZ characterisation with ultrasonic interval velocity measurements in the Meuse/Haute-Marne URL, performed between depth of 85 m and 504 m (K. Schuster, H.J. Alheid); the clay formation at the Meuse Haute Marne URL: evaluation of the impact of resin filled slots on flow paths characteristics within the EDZ (J.M. Lavanchy, J. Croise, R. Schwarz, G. Armand, M. Cruchaudet); the characterisation and evolution of EDZ by extraction and analyse of noble gases in pore waters in the Meuse/Haute Marne URL site (B. Lavielle, B. Thomas, E. Gilabert); in-situ gas test for the characterisation of Excavation Disturbed Zone at the Meuse/Haute Marne URL (H. Shao, K. Schuster, J. Soennke, V. Braeuer); and the flow and reactive

  16. Web-Browsing Competencies of Pre-Service Adult Facilitators: Implications for Curriculum Transformation and Distance Learning

    Science.gov (United States)

    Theresa, Ofoegbu; Ugwu, Agboeze Matthias; Ihebuzoaju, Anyanwu Joy; Uche, Asogwa

    2013-01-01

    The study investigated the Web-browsing competencies of pre-service adult facilitators in the southeast geopolitical zone of Nigeria. Survey design was adopted for the study. The population consists of all pre-service adult facilitators in all the federal universities in the southeast geopolitical zone of Nigeria. Accidental sampling technique was…

  17. Management of coastal zone vegetation

    Digital Repository Service at National Institute of Oceanography (India)

    Untawale, A.G.

    stream_size 14 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

  18. Instrumentation for coastal zone management

    Digital Repository Service at National Institute of Oceanography (India)

    Joseph, A.

    stream_size 11 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

  19. Zone refining of plutonium metal

    Energy Technology Data Exchange (ETDEWEB)

    Blau, Michael S. [Univ. of Idaho, Moscow, ID (United States)

    1994-08-01

    The zone refining process was applied to Pu metal containing known amounts of impurities. Rod specimens of plutonium metal were melted into and contained in tantalum boats, each of which was passed horizontally through a three-turn, high-frequency coil in such a manner as to cause a narrow molten zone to pass through the Pu metal rod 10 times. The impurity elements Co, Cr, Fe, Ni, Np, U were found to move in the same direction as the molten zone as predicted by binary phase diagrams. The elements Al, Am, and Ga moved in the opposite direction of the molten zone as predicted by binary phase diagrams. As the impurity alloy was zone refined, {delta}-phase plutonium metal crystals were produced. The first few zone refining passes were more effective than each later pass because an oxide layer formed on the rod surface. There was no clear evidence of better impurity movement at the slower zone refining speed. Also, constant or variable coil power appeared to have no effect on impurity movement during a single run (10 passes). This experiment was the first step to developing a zone refining process for plutonium metal.

  20. Volcanic Zone, New Zealand

    Directory of Open Access Journals (Sweden)

    Graham J. Weir

    2001-01-01

    Full Text Available A conceptual model of the Taupo Volcanic Zone (TVZ is developed, to a depth of 25 km, formed from three constant density layers. The upper layer is formed from eruption products. A constant rate of eruption is assumed, which eventually implies a constant rate of extension, and a constant rate of volumetric creation in the middle and bottom layers. Tectonic extension creates volume which can accomodate magmatic intrusions. Spreading models assume this volume is distributed throughout the whole region, perhaps in vertical dykes, whereas rifting models assume the upper crust is thinned and the volume created lies under this upper crust. Bounds on the heat flow from such magmatic intrusions are calculated. Heat flow calculations are performed and some examples are provided which match the present total heat output from the TVZ of about 4200 MW, but these either have extension rates greater than the low values of about 8 ± 4 mm/a being reported from GPS measurements, or else consider extension rates in the TVZ to have varied over time.

  1. Physiological and behavioural correlates of life-history variation : a comparison between tropical and temperate zone House Wrens

    NARCIS (Netherlands)

    Tieleman, BI; Lasky, [No Value; Mauck, RA; Visser, GH; Williams, JB; Lasky, J.R.; Kozłowski, Jan

    2006-01-01

    1. We studied physiological, behavioural and demographic traits of House Wrens (Troglodytes aedon) in tropical Panama and temperate zone Ohio to explore the hypothesis that tropical birds with higher adult survival rates invest less in annual reproduction than their temperate zone counterparts. 2. C

  2. Golli myelin basic proteins stimulate oligodendrocyte progenitor cell proliferation and differentiation in remyelinating adult mouse brain.

    Science.gov (United States)

    Paez, Pablo M; Cheli, Veronica T; Ghiani, Cristina A; Spreuer, Vilma; Handley, Vance W; Campagnoni, Anthony T

    2012-07-01

    Golli myelin basic proteins are necessary for normal myelination, acting via voltage and store-dependent Ca(2+) entry at multiple steps during oligodendrocyte progenitor cell (OPC) development. To date nothing is known regarding the role of golli proteins in demyelination or remyelination events. Here the effects of golli ablation and overexpression in myelin loss and recovery were examined using the cuprizone (CPZ) model of demyelination/remyelination. We found severe demyelination in the corpus callosum (CC) of golli-overexpressing mice (JOE) during the CPZ treatment, which was accompanied by an increased number of reactive astrocytes and activation of microglia/macrophages. During demyelination of JOE brains, a significant increase in the number of proliferating OPCs was found in the CC as well as in the subventricular zone, and our data indicate that these progenitors matured and fully remyelinated the CC of JOE animals after CPZ withdrawal. In contrast, in the absence of golli (golli-KO mice) delayed myelin loss associated with a smaller immune response, and a lower number of OPCs was found in these mice during the CPZ treatment. Furthermore, incomplete remyelination was observed after CPZ removal in large areas of the CC of golli-KO mice, reflecting irregular recovery of the oligodendrocyte population and subsequent myelin sheath formation. Our findings demonstrate that golli proteins sensitize mature oligodendrocytes to CPZ-induced demyelination, while at the same time stimulate the proliferation/recruitment of OPCs during demyelination, resulting in accelerated remyelination.

  3. Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate.

    Science.gov (United States)

    Cavaliere, F; Urra, O; Alberdi, E; Matute, C

    2012-02-02

    We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination.

  4. Newly generated cells are increased in hippocampus of adult mice lacking a serine protease inhibitor

    Directory of Open Access Journals (Sweden)

    Sticker Melanie

    2010-06-01

    Full Text Available Abstract Background Neurogenesis in the hippocampal dentate gyrus and the subventricular zone occurs throughout the life of mammals and newly generated neurons can integrate functionally into established neuronal circuits. Neurogenesis levels in the dentate gyrus are modulated by changes in the environment (enrichment, exercise, hippocampal-dependent tasks, NMDA receptor (NMDAR activity, sonic hedgehog (SHH and/or other factors. Results previously, we showed that Protease Nexin-1 (PN-1, a potent serine protease inhibitor, regulates the NMDAR availability and activity as well as SHH signaling. Compared with wild-type (WT, we detected a significant increase in BrdU-labeled cells in the dentate gyrus of mice lacking PN-1 (PN-1 -/- both in controls and after running exercise. Patched homologue 1 (Ptc1 and Gli1 mRNA levels were higher and Gli3 down-regulated in mutant mice under standard conditions and to a lesser extent after running exercise. However, the number of surviving BrdU-positive cells did not differ between WT and PN-1 -/- animals. NMDAR availability was altered in the hippocampus of mutant animals after exercise. Conclusion All together our results indicate that PN-1 controls progenitors proliferation through an effect on the SHH pathway and suggest an influence of the serpin on the survival of newly generated neurons through modulation of NMDAR availability.

  5. Relative importance of sexual and asexual reproduction for range expansion of Spartina alterniflora in different tidal zones on Chinese coast

    Science.gov (United States)

    Liu, Huiyu; Lin, Zhenshan; Zhang, Mingyang; Qi, Xiangzhen

    2017-02-01

    In this paper, based on spatially explicit individual-based model and global sensitivity analysis, the relative importance of sexual and asexual reproduction for range expansion of Spartina alterniflora in different tidal zones during different invasion stages has been revealed. The results showed that: 1) sexual reproduction is thought to accelerate the range expansion in middle and high tidal zones; 2) seed dispersal and adult survival rate are the two most important for range expansion of S. alterniflora during most invasion stages in all tidal zones. However, in high tidal zone, the importance of seed dispersal distance is much less than in low and middle tidal zones, and that of sexual reproduction is also great, which cannot be ignored. In middle tidal zone, the importance of adult survival rate is less important than in high and low tidal zones, and is very close to asexual reproduction. Moreover, there are significant fluctuations among the importance of different parameters except seed dispersal distance, indicating strong interactions. 3) the importance of adult survival rate and asexual reproduction is much greater than seed dispersal distance during early invasion. Especially, their importance is much higher during early and middle invasion stages in high tidal zone. During early invasion stages, the interactions among different parameters are very strong. To enhance the invasion control efficiency, it is necessary to take different control measures according to different tidal zones and invasion stages.

  6. 49 CFR 71.8 - Mountain zone.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Mountain zone. 71.8 Section 71.8 Transportation Office of the Secretary of Transportation STANDARD TIME ZONE BOUNDARIES § 71.8 Mountain zone. The fourth zone, the mountain standard time zone, includes that part of the United States that is west of...

  7. Formalized morphostructural zoning of the mountain zone of the Andes

    Energy Technology Data Exchange (ETDEWEB)

    Gabrielov, A.M.; Gvishiani, A.D.; Zhidkov, M.P.

    1982-01-01

    A plan is presented for morphostructural zoning of the Andes compiled according to formalized signs for purposes of seismic forecasting. Characteristics are presented for the basic morphostructural subdivisions of the Andes.

  8. Proliferation and migration in vivo of neural precursor cells in adult rat brain following fluid percussion injury%成年大鼠脑损伤后神经前体细胞的增殖及迁移

    Institute of Scientific and Technical Information of China (English)

    张相彤; 王忠诚; 董丽萍; 张亚卓; 戴钦舜

    2005-01-01

    (GFAP)+/Brdu+ and GFAP-/Brdu+ cells in the rat brain of each group at various time points.with the control group, nestin-positive cells in the cortex, hippocampus and subventricular zone on the injured side was obviously increased at 1day after FPI (3.1±1.1 vs 0, 5.5±0.9 vs 1.3±0.8 and 8.1±0.9 vs 2.3±0.8 in each visual field, respectively, P<0.05), reaching the peak on day 7 (7.5±1.2,10.2±1.5, and 13.6±1.2 in each visual field, respectively) and disappeared BrdU-positive cells in the cortex, hippocampus and subventricular zone on the injured side increased to the highest level 3 days after FPI (12.6±1.5,9.9±1.1, and 13.4±1.0 in each visual field, respectively), but gradually delar zone gradually migrated to the opposite side across the corpus callosum.CONCLUSION: FPI can stimulate the proliferation and migration of neural progenitor cells in adult rat brain, such as in the cortex, hippocampus and subventricular zone, where the nestin-positive cells is the most 7 days after the injury, but BrdU-positive cells is the most 3 days after the injury.%背景:成年哺乳类动物中枢神经系统存有神经前体细胞,其基本生物学特性主要包括多向细胞分化和维持自身数量稳定.目的:观察中枢神经系统损伤后神经前体细胞增殖和迁移的反应过程,探讨神经前体细胞在中枢神经系统损伤修复中的作用,设计:随机对照实验.单位:北京市神经外科研究所病理生理研究室.材料:实验在北京市神经外科研究所病理生理研究室完成.选择成年Wistar大鼠67只,随机分为正常对照组7只,损伤后1,3,7,14,30 d组,每个损伤组12只.以上每个损伤组再随机分为人工脑脊液组2只,碱性成纤维细胞生长因子组5只和神经营养因子-3组5只.方法:各损伤组制作液压冲击性脑损伤模型,正常对照组仅开颅,不致伤.各损伤组每次腹腔内注射BrdU 50 mg/kg,处死前2 h注入最后一次,其中损伤后1 d和3 d组每天注入3

  9. Chaotic zones around gravitating binaries

    CERN Document Server

    Shevchenko, Ivan I

    2014-01-01

    The extent of the continuous zone of chaotic orbits of a small-mass tertiary around a system of two gravitationally bound bodies (a double star, a double black hole, a binary asteroid, etc.) is estimated analytically, in function of the tertiary's orbital eccentricity. The separatrix map theory is used to demonstrate that the central continuous chaos zone emerges due to overlapping of the orbital resonances corresponding to the integer ratios p:1 between the tertiary and the binary periods. The binary's mass ratio, above which such a chaotic zone is universally present, is also estimated.

  10. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  11. Adult flatfoot.

    Science.gov (United States)

    Toullec, E

    2015-02-01

    Adult flatfoot is defined as a flattening of the medial arch of the foot in weight-bearing and lack of a propulsive gait. The 3 lesion levels are the talonavicular, tibiotarsal and midfoot joints. The subtalar joint is damaged by the consequent rotational defects. Clinical examination determines deformity and reducibility, and assesses any posterior tibialis muscle deficit, the posterior tibialis tendon and spring ligament being frequently subject to degenerative lesions. Radiographic examination in 3 incidences in weight-bearing is essential, to determine the principal level of deformity. Tendon (posterior tibialis tendon) and ligamentous lesions (spring ligament and interosseous ligament) are analyzed on MRI or ultrasound. In fixed deformities, CT explores for arthritic evolution or specific etiologies. 3D CT reconstruction can analyze bone and joint morphology and contribute to the planning of any osteotomy. Medical management associates insoles and physiotherapy. Acute painful flatfoot requires strict cast immobilization. Surgical treatment associates numerous combinations of procedures, currently under assessment for supple flatfoot: for the hindfoot: medial slide calcaneal osteotomy, calcaneal lengthening osteotomy, or arthroereisis; for the midfoot: arthrodesis on one or several rays, or first cuneiform or first metatarsal osteotomy; for the ankle: medial collateral ligament repair with tendon transfer. Fixed deformities require arthrodesis of one or several joint-lines in the hindfoot; for the ankle, total replacement after realignment of the foot, or tibiotalocalcaneal fusion or ankle and hindfoot fusion; and, for the midfoot, cuneonavicular or cuneometatarsal fusion. Tendinous procedures are often associated. Specific etiologies may need individualized procedures. In conclusion, adult flatfoot tends to be diagnosed and managed too late, with consequent impact on the ankle, the management of which is complex and poorly codified.

  12. ShoreZone Survey Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset is a point file showing GPS trackline data collected during a ShoreZone aerial imaging survey. This flight trackline is recorded at 1-second intervals...

  13. In situ vadose zone bioremediation.

    Science.gov (United States)

    Höhener, Patrick; Ponsin, Violaine

    2014-06-01

    Contamination of the vadose zone with various pollutants is a world-wide problem, and often technical or economic constraints impose remediation without excavation. In situ bioremediation in the vadose zone by bioventing has become a standard remediation technology for light spilled petroleum products. In this review, focus is given on new in situ bioremediation strategies in the vadose zone targeting a variety of other pollutants such as perchlorate, nitrate, uranium, chromium, halogenated solvents, explosives and pesticides. The techniques for biostimulation of either oxidative or reductive degradation pathways are presented, and biotransformations to immobile pollutants are discussed in cases of non-degradable pollutants. Furthermore, research on natural attenuation in the vadose zone is presented.

  14. Offshore Wind Technology Depth Zones

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Coastal bathymetric depth, measured in meters at depth values of: -30, -60, -900 Shallow Zone (0-30m): Technology has been demonstrated on a commercial scale at...

  15. NEPR Geographic Zone Map 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This geographic zone map was created by interpreting satellite and aerial imagery, seafloor topography (bathymetry model), and the new NEPR Benthic Habitat Map...

  16. Development Zones Flourish in Beijing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Based on the Beijing Municipal Government's plans for developing the city and neighboring suburbs,and after more than 10 years in development,the Beijing Development Zones have taken shape,each with their own characteristics.

  17. Obsessive Compulsive Disorder among Adults

    Science.gov (United States)

    ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ... Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among Adults - Bulimia Nervosa Eating Disorders ...

  18. Demarcation of secondary hyperalgesia zones

    DEFF Research Database (Denmark)

    Ringsted, Thomas K; Enghuus, Casper; Petersen, Morten A;

    2015-01-01

    of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). NEW METHOD: The study was a two...... presented. CONCLUSIONS: This is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used....

  19. The global aftershock zone

    Science.gov (United States)

    Parsons, Thomas E.; Margaret Segou,; Warner Marzocchi,

    2014-01-01

    The aftershock zone of each large (M ≥ 7) earthquake extends throughout the shallows of planet Earth. Most aftershocks cluster near the mainshock rupture, but earthquakes send out shivers in the form of seismic waves, and these temporary distortions are large enough to trigger other earthquakes at global range. The aftershocks that happen at great distance from their mainshock are often superposed onto already seismically active regions, making them difficult to detect and understand. From a hazard perspective we are concerned that this dynamic process might encourage other high magnitude earthquakes, and wonder if a global alarm state is warranted after every large mainshock. From an earthquake process perspective we are curious about the physics of earthquake triggering across the magnitude spectrum. In this review we build upon past studies that examined the combined global response to mainshocks. Such compilations demonstrate significant rate increases during, and immediately after (~ 45 min) M > 7.0 mainshocks in all tectonic settings and ranges. However, it is difficult to find strong evidence for M > 5 rate increases during the passage of surface waves in combined global catalogs. On the other hand, recently published studies of individual large mainshocks associate M > 5 triggering at global range that is delayed by hours to days after surface wave arrivals. The longer the delay between mainshock and global aftershock, the more difficult it is to establish causation. To address these questions, we review the response to 260 M ≥ 7.0 shallow (Z ≤ 50 km) mainshocks in 21 global regions with local seismograph networks. In this way we can examine the detailed temporal and spatial response, or lack thereof, during passing seismic waves, and over the 24 h period after their passing. We see an array of responses that can involve immediate and widespread seismicity outbreaks, delayed and localized earthquake clusters, to no response at all. About 50% of the

  20. Occurrence of new neurons in the piriform cortex.

    Science.gov (United States)

    Yuan, Ti-Fei; Liang, Yu-Xiang; So, Kwok-Fai

    2014-01-01

    Adult neurogenesis has been well studied in hippocampus and subventricular zone (SVZ); while this is much less appreciated in other brain regions, including amygdala, hypothalamus, and piriform cortex (PC). The present review aims at summarizing recent advances on the occurrence of new neurons in the PC, their potential origin, and migration route from the SVZ. We further discuss the relevant implications in olfactory dysfunction accompanying the neurodegenerative diseases.

  1. Adult Still's disease

    Science.gov (United States)

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  2. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  3. Zone and double zone diagrams in abstract spaces

    CERN Document Server

    Reem, Daniel

    2007-01-01

    A zone diagram of order $n$ is a relatively new concept which was first defined and studied by T. Asano, J. Matousek and T. Tokuyama. It can be interpreted as a state of equilibrium between $n$ mutually hostile kingdoms. Formally, it is a fixed point of a certain mapping. These authors considered the Euclidean plane and proved the existence and uniqueness of zone diagrams there. In the present paper we generalize this concept in various ways. We consider $m$-spaces (a simple generalization of metric spaces) and prove some existence and (non)uniqueness results there. In contrast to previous works, our proofs are based on purely order theoretic arguments. Many explicit examples are given, and some of them illustrate new phenomena which occur in the general case. We also re-interpret zone diagrams as a stable configuration in a certain combinatorial game, and provide an algorithm for finding this configuration in a particular case.

  4. SEMIAUTOMATIC DETECTION OF TUMORAL ZONE

    Directory of Open Access Journals (Sweden)

    Ezzeddine Zagrouba

    2011-05-01

    Full Text Available This paper describes a robust method based on the cooperation of fuzzy classification and regions segmentation algorithms, in order to detect the tumoral zone in the brain Magnetic Resonance Imaging (MRI. On one hand, the classification in fuzzy sets is done by the Fuzzy C-Means algorithm (FCM, where a study of its different parameters and its complexity has been previously realised, which led us to improve it. On the other hand, the segmentation in regions is obtained by an hierarchical method through adaptive thresholding. Then, an operator expert selects a germ in the tumoral zone, and the class containing the sick zone is localised in return for the FCM algorithm. Finally, the superposition of the two partitions of the image will determine the sick zone. The originality of our approach is the parallel exploitation of different types of information in the image by the cooperation of two complementary approaches. This allows us to carry out a pertinent approach for the detection of sick zone in MRI images.

  5. Plumes in stellar convection zones

    CERN Document Server

    Zahn, J P

    1999-01-01

    All numerical simulations of compressible convection reveal the presence of strong downwards directed flows. Thanks to helioseismology, such plumes have now been detected also at the top of the solar convection zone, on super- granular scales. Their properties may be crudely described by adopting Taylor's turbulent entrainment hypothesis, whose validity is well established under various conditions. Using this model, one finds that the strong density stratification does not prevent the plumes from traversing the whole convection zone, and that they carry upwards a net energy flux (Rieutord & Zahn 1995). They penetrate to some extent in the adjacent stable region, where they establish a nearly adiabatic stratification. These plumes have a strong impact on the dynamics of stellar convection zones, and they play probably a key role in the dynamo mechanism.

  6. Cell proliferation and neurogenesis in adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Olivia L Bordiuk

    Full Text Available Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ, and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  7. 76 FR 7107 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2011-02-09

    ...-0997 New York, NY Security Zones (Part 165).... 9/23/2008 USCG-2008-0998 Puerto Rico Safety Zones (Part...-0358 Puerto Rico Safety Zones (Part 165)...... 5/31/2009 USCG-2009-0360 Cincinnati, OH Safety Zones...-1042 Baton Rouge, LA Safety Zones (Part 165)...... 12/4/2009 USCG-2009-1043 South Padre Island,...

  8. Effect of Opioid on Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-01-01

    Full Text Available During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs’ effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal’s opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse.

  9. ISOLDE target zone control room

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  10. Land Governance as Grey Zone

    DEFF Research Database (Denmark)

    Kjær, Anne Mette

    2017-01-01

    demonstrates that in Uganda, the need to maintain the ruling coalition in a clientelist political settlement to build electoral support, and the desire to attract economic investors, constitute political incentives to maintain land governance as a grey zone, even if there is apparent political...

  11. Cerebellar Zones: A Personal History

    NARCIS (Netherlands)

    J. Voogd (Jan)

    2011-01-01

    textabstractCerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because thr

  12. Building a Subduction Zone Observatory

    Science.gov (United States)

    Gomberg, Joan S.; Bodin, Paul; Bourgeois, Jody; Cashman, Susan; Cowan, Darrel; Creager, Kenneth C.; Crowell, Brendan; Duvall, Alison; Frankel, Arthur; Gonzalez, Frank; Houston, Heidi; Johnson, Paul; Kelsey, Harvey; Miller, Una; Roland, Emily C.; Schmidt, David; Staisch, Lydia; Vidale, John; Wilcock, William; Wirth, Erin

    2016-01-01

    Subduction zones contain many of Earth’s most remarkable geologic structures, from the deepest oceanic trenches to glacier-covered mountains and steaming volcanoes. These environments formed through spectacular events: Nature’s largest earthquakes, tsunamis, and volcanic eruptions are born here.

  13. ShoreZone Mapped Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set is a polyline file of mapped ShoreZone units which correspond with data records found in the Unit, Xshr, BioUnit, and BioBand tables of this...

  14. Objects as Temporary Autonomous Zones

    Directory of Open Access Journals (Sweden)

    Tim Morton

    2011-09-01

    Full Text Available From Hakim Bey's instructions on creating temporary autonomous zones we see an oscillation "between performance art and politics, circus clowning and revolution." In this essay Tim Morton discusses anarchist politics as, "the creation of fresh objects in a reality without a top or a bottom object, or for that matter a middle object."

  15. Objects as Temporary Autonomous Zones

    OpenAIRE

    Tim Morton

    2011-01-01

    From Hakim Bey's instructions on creating temporary autonomous zones we see an oscillation "between performance art and politics, circus clowning and revolution." In this essay Tim Morton discusses anarchist politics as, "the creation of fresh objects in a reality without a top or a bottom object, or for that matter a middle object."

  16. CHAOTIC ZONES AROUND GRAVITATING BINARIES

    Energy Technology Data Exchange (ETDEWEB)

    Shevchenko, Ivan I., E-mail: iis@gao.spb.ru [Pulkovo Observatory of the Russian Academy of Sciences, Pulkovskoje ave. 65, St. Petersburg 196140 (Russian Federation)

    2015-01-20

    The extent of the continuous zone of chaotic orbits of a small-mass tertiary around a system of two gravitationally bound primaries of comparable masses (a binary star, a binary black hole, a binary asteroid, etc.) is estimated analytically, as a function of the tertiary's orbital eccentricity. The separatrix map theory is used to demonstrate that the central continuous chaos zone emerges (above a threshold in the primaries' mass ratio) due to overlapping of the orbital resonances corresponding to the integer ratios p:1 between the tertiary and the central binary periods. In this zone, the unlimited chaotic orbital diffusion of the tertiary takes place, up to its ejection from the system. The primaries' mass ratio, above which such a chaotic zone is universally present at all initial eccentricities of the tertiary, is estimated. The diversity of the observed orbital configurations of biplanetary and circumbinary exosystems is shown to be in accord with the existence of the primaries' mass parameter threshold.

  17. Priority Education Zones in Mauritius

    Science.gov (United States)

    Kumar, Mahadeo Santosh; Gurrib, Mahomed Aniff

    2008-01-01

    This article discusses the Priority Education Zones project (ZEP) in Mauritius. The original and innovative dimensions of the project are described, together with the difficulties encountered during the setting-up of the ZEP schools. The article covers five main issues: the status of the ZEP project; the minimal conditions for success; the…

  18. Zone refining of plutonium metal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    The purpose of this study was to investigate zone refining techniques for the purification of plutonium metal. The redistribution of 10 impurity elements from zone melting was examined. Four tantalum boats were loaded with plutonium impurity alloy, placed in a vacuum furnace, heated to 700{degrees}C, and held at temperature for one hour. Ten passes were made with each boat. Metallographic and chemical analyses performed on the plutonium rods showed that, after 10 passes, moderate movement of certain elements were achieved. Molten zone speeds of 1 or 2 inches per hour had no effect on impurity element movement. Likewise, the application of constant or variable power had no effect on impurity movement. The study implies that development of a zone refining process to purify plutonium is feasible. Development of a process will be hampered by two factors: (1) the effect on impurity element redistribution of the oxide layer formed on the exposed surface of the material is not understood, and (2) the tantalum container material is not inert in the presence of plutonium. Cold boat studies are planned, with higher temperature and vacuum levels, to determine the effect on these factors. 5 refs., 1 tab., 5 figs.

  19. Adult Neurogenesis in Drosophila

    OpenAIRE

    Ismael Fernández-Hernández; Christa Rhiner; Eduardo Moreno

    2013-01-01

    Adult neurogenesis has been linked to several cognitive functions and neurological disorders. Description of adult neurogenesis in a model organism like Drosophila could facilitate the genetic study of normal and abnormal neurogenesis in the adult brain. So far, formation of new neurons has not been detected in adult fly brains and hence has been thought to be absent in Drosophila. Here, we used an improved lineage-labeling method to show that, surprisingly, adult neurogenesis occurs in the m...

  20. Unsaturated Zone and Saturated Zone Transport Properties (U0100)

    Energy Technology Data Exchange (ETDEWEB)

    J. Conca

    2000-12-20

    This Analysis/Model Report (AMR) summarizes transport properties for the lower unsaturated zone hydrogeologic units and the saturated zone at Yucca Mountain and provides a summary of data from the Busted Butte Unsaturated Zone Transport Test (UZTT). The purpose of this report is to summarize the sorption and transport knowledge relevant to flow and transport in the units below Yucca Mountain and to provide backup documentation for the sorption parameters decided upon for each rock type. Because of the complexity of processes such as sorption, and because of the lack of direct data for many conditions that may be relevant for Yucca Mountain, data from systems outside of Yucca Mountain are also included. The data reported in this AMR will be used in Total System Performance Assessment (TSPA) calculations and as general scientific support for various Process Model Reports (PMRs) requiring knowledge of the transport properties of different materials. This report provides, but is not limited to, sorption coefficients and other relevant thermodynamic and transport properties for the radioisotopes of concern, especially neptunium (Np), plutonium (Pu), Uranium (U), technetium (Tc), iodine (I), and selenium (Se). The unsaturated-zone (UZ) transport properties in the vitric Calico Hills (CHv) are discussed, as are colloidal transport data based on the Busted Butte UZTT, the saturated tuff, and alluvium. These values were determined through expert elicitation, direct measurements, and data analysis. The transport parameters include information on interactions of the fractures and matrix. In addition, core matrix permeability data from the Busted Butte UZTT are summarized by both percent alteration and dispersion.

  1. TASK 2: QUENCH ZONE SIMULATION

    Energy Technology Data Exchange (ETDEWEB)

    Fusselman, Steve

    2015-09-30

    Aerojet Rocketdyne (AR) has developed an innovative gasifier concept incorporating advanced technologies in ultra-dense phase dry feed system, rapid mix injector, and advanced component cooling to significantly improve gasifier performance, life, and cost compared to commercially available state-of-the-art systems. A key feature of the AR gasifier design is the transition from the gasifier outlet into the quench zone, where the raw syngas is cooled to ~ 400°C by injection and vaporization of atomized water. Earlier pilot plant testing revealed a propensity for the original gasifier outlet design to accumulate slag in the outlet, leading to erratic syngas flow from the outlet. Subsequent design modifications successfully resolved this issue in the pilot plant gasifier. In order to gain greater insight into the physical phenomena occurring within this zone, AR developed a cold flow simulation apparatus with Coanda Research & Development with a high degree of similitude to hot fire conditions with the pilot scale gasifier design, and capable of accommodating a scaled-down quench zone for a demonstration-scale gasifier. The objective of this task was to validate similitude of the cold flow simulation model by comparison of pilot-scale outlet design performance, and to assess demonstration scale gasifier design feasibility from testing of a scaled-down outlet design. Test results did exhibit a strong correspondence with the two pilot scale outlet designs, indicating credible similitude for the cold flow simulation device. Testing of the scaled-down outlet revealed important considerations in the design and operation of the demonstration scale gasifier, in particular pertaining to the relative momentum between the downcoming raw syngas and the sprayed quench water and associated impacts on flow patterns within the quench zone. This report describes key findings from the test program, including assessment of pilot plant configuration simulations relative to actual

  2. Young Adult Literature for Young Adult Males.

    Science.gov (United States)

    Gill, Sam D.

    1999-01-01

    Argues that young adult literature can play a significant role in the emotional and mental health of an adolescent as well as help young males become more literate. Offers a 19-item annotated list of young adult novels with male protagonists, sorted by themes: nature and adventure stories, sports stories, genre stories, historical stories, and…

  3. Clueless? Adult Mysteries with Young Adult Appeal.

    Science.gov (United States)

    Charles, John; Morrison, Joanna

    1997-01-01

    Presents a list of adult mystery titles for young adult readers. Includes first titles in a series (for reading in order); new and lesser-known mystery authors' works are the focus. Annotations include plot summary. The rest of each annotation is for professional use (includes date and name of award bestowed). (AEF)

  4. Zone Denmark - gasell Taanist / Reet Krause

    Index Scriptorium Estoniae

    Krause, Reet, 1967-

    2006-01-01

    Taanis Viborgis asuva firma Zone Company Denmark, kaubamärgi Zone Denmark ja firma disainerite tutvustus. Ettevõte valmistab disainitooteid roostevabast terasest, klaasist, puidust, kummist jm. Disainer Naja Utzon Popov endast, oma loomingust

  5. United States Stateplane Zones - NAD83

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1983) represents the State Plane Coordinate System (SPCS) Zones for the 1983 North American Datum within United States.

  6. United States Stateplane Zones - NAD27

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1927) represents the State Plane Coordinate System (SPCS) Zones for the 1927 North American Datum within United States.

  7. GIS modeling of introduction zones in Sochi

    Directory of Open Access Journals (Sweden)

    Annenkova Irina Vladimirovna

    2014-11-01

    Defined the mean monthly temperature and precipitation for each zone. The diagram shows the dependence of the probability distribution of the three groups resistance from the mean annual temperature and mean annual precipitation. Describes the climatic conditions of the zones.

  8. Zoning, 2004, East Baton Rouge Parish, Louisiana

    Data.gov (United States)

    Louisiana Geographic Information Center — This is a graphical polygon dataset depicting the zoning boundaries of the East Baton Rouge Parish of the State of Louisiana. Zoning can be defined as the range of...

  9. Experiential reflective learning and comfort zone

    Directory of Open Access Journals (Sweden)

    Jan Nehyba

    2011-09-01

    Full Text Available The article deals with the issue of experiential reflective learning. Firstlyit aims to discuss the concept of comfort zone in this area. It goes beyond the usualdefinition of the domestic comfort zone and it reflects in terms of experiential reflectivelearning in the world. The conclusions point to possible parallels with the concept ofcomfort zones and K. Lewin theory. Overall, the article focuses on topics that help toexpand the view on the issue of comfort zone.

  10. Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells.

    Science.gov (United States)

    Kornblum, H I; Yanni, D S; Easterday, M C; Seroogy, K B

    2000-01-01

    The epidermal growth factor receptor family consists of four related tyrosine kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, ErbB3, and ErbB4. These receptors are capable of extensive cross-activation upon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by proliferating cells in the central nervous system (CNS), including multipotent CNS stem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germinal epithelia of the developing rat brain using in situ hybridization. ErbB2 and ErbB4 mRNAs were widely distributed within the germinal zones as early as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by subventricular zone cells, in the regions where these specialized germinal epithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbrain. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, ErbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Heregulin-beta1, a neuregulin, had no effect on the proliferative capacity of neurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our in vitro data do not support a role for neuregulins in proliferation, per se, of CNS stem cells.

  11. 46 CFR 76.35-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Zoning. 76.35-5 Section 76.35-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Manual Alarm System, Details § 76.35-5 Zoning. (a) The zoning of the manual alarm system shall meet the same requirements...

  12. 46 CFR 76.23-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Zoning. 76.23-5 Section 76.23-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Manual Sprinkling System, Details § 76.23-5 Zoning. (a) Separate zones may be used for each deck, and on any...

  13. 46 CFR 76.33-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Zoning. 76.33-5 Section 76.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-5 Zoning. (a) The smoke detecting system shall be divided into separate zones...

  14. Export Processing Zones and Global Class Formation

    NARCIS (Netherlands)

    Neveling, Patrick

    2015-01-01

    This chapter is concerned with one of the most striking developments in the global political economy of capitalism after the Second World War; the rise of export processing zones and special economic zones. Building on long-term ethnohistorical research on the zones’ global spread from one zone in P

  15. Adults Role in Bullying

    Science.gov (United States)

    Notar, Charles E.; Padgett, Sharon

    2013-01-01

    Do adults play a role in bullying? Do parents, teachers, school staff, and community adult leaders influence bullying behavior in children and teenagers? This article will focus on research regarding all adults who have almost daily contact with children and teens and their part in how bullying is identified, addressed, and prevented. This article…

  16. Dimensions of Adult Learning

    Science.gov (United States)

    Foley, Griff, Ed.

    2004-01-01

    This broad introduction to adult and postcompulsory education offers an overview of the field for students, adult educators and workplace trainers. The book establishes an analytical framework to emphasize the nature of learning and agency of learners; examines the core knowledge and skills that adult educators need; discusses policy, research and…

  17. Adult Education in Turkey

    Science.gov (United States)

    Miser, Rifat; Ural, Ozana; Ünlühisarýklý, Özlem

    2013-01-01

    This study investigates the situation and practices of adult education in Turkey in terms of (a) participants, (b) providers, and (c) program areas. The data were derived from published statistical data and one-to-one interaction with adult education providers when such data are unavailable. Turkey has a long tradition of adult education with…

  18. Canadian Adult Basic Education.

    Science.gov (United States)

    Brooke, W. Michael, Comp.

    "Trends," a publication of the Canadian Association for Adult Education, is a collection of abstracts on selected subjects affecting adult education; this issue is on adult basic education (ABE). It covers teachers and teacher training, psychological factors relating to the ABE teacher and students, manuals for teachers, instructional…

  19. The Adult Experience.

    Science.gov (United States)

    Belsky, Janet

    The 14 chapters of this textbook chronicle adult development from youth through old age, emphasizing both research and interviews with adults at various stages in their lives. Topics covered include the following: (1) the academic field of adult development; (2) theories and research methods; (3) aging and disease prevention; (4) sexuality and…

  20. 40 CFR 265.278 - Unsaturated zone (zone of aeration) monitoring.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Unsaturated zone (zone of aeration) monitoring. 265.278 Section 265.278 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., STORAGE, AND DISPOSAL FACILITIES Land Treatment § 265.278 Unsaturated zone (zone of aeration)...

  1. Chronic obstructive pulmonary disease - adults - discharge

    Science.gov (United States)

    COPD - adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - discharge; Bronchitis - ...

  2. The stretch zone of automotive steel sheets

    Indian Academy of Sciences (India)

    Ľ Ambriško; L Pešek

    2014-04-01

    The paper deals with an experimental determination of the stretch zone dimensions in the notch tip in thin steel sheets. The stretch zone dimensions depend on steel grade, on the rolling direction as well as on the loading rate. Stretch zones were observed and measured on three steel grades. Fracture area and stretch zones were analysed by SEM. Stable crack growth was monitored by videoextensometry techniques on CT (Compact Tension) specimens. Specimens were loaded under two loading rates by eccentric tension, whereby the deformation in the notch surrounding area was recorded using a non-contact measurement–videoextensometry technique. Linear relation between the stretch zone dimensions was determined.

  3. Investigations of Near-Zone Doppler Effects.

    Science.gov (United States)

    Prouty, Dale Austen

    Far away from an electromagnetic source the normal Doppler shifts in frequency occur--a red shift for receding and a blue shift for approaching. As indicated by previous work with an infinitesimal dipole, different frequency shifts occur when the source and observer move closer together, into the near-zone. These "near-zone Doppler effects" are investigated for general sources and subsequently two specific examples are presented. The general results show that near-zone shifts are similar to far-zone shifts, but the local phase velocity must be used, i.e. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI). In the far zone the phase velocity is the speed of light; in the near zone it differs. Fundamentally, the distance between surfaces of constant phase in the near zone is changed. The surfaces of constant phase for the waves are no longer spherical, but more ellipsoidal or spheroidal, so that a moving observer sees a different frequency shift. Two specific examples are presented to indicate the actual magnitude of near-zone effects. The examples include a prolate spheroidal antenna and a circular aperture. Once the magnitude of the effects is determined, the measurability of near-zone Doppler effects is discussed. The investigation concentrates on Fresnel zone effects due to the measurement problem. Finally, it is shown that for an electrically large wire antenna (the spheroidal example) near-zone Doppler effects are measurable.

  4. Holdridge life zone physical inconsistency

    Science.gov (United States)

    Martínez, A., Sr.; Ochoa, A.

    2015-12-01

    Life zones is a very used classification system, developed by L.R. Holdridge in 1967, used to discern why plants have different adaptation mechanism to their surrounding environment. In this paper, the relation between potential evapotranspiration rate (ETr ), anual precipitation (P ) and biotemperature (Tb ) in the Holdridge triangle, is parametrized (P = (500/9)*ETr) to evaluate if the rain process is conserved in Colombia. Further, an adiabatic ascent of air with diurnal and interannual variability, and cluster analysis is view as a classification example of the advantage of using physical process to evaluate the plants adaptation mechanisms . The most inconsistency life zones are situated in the rainiest places of Colombian pacific costs in tropical latitudinal region, are non-exist places in holdridge triangle with annual biotemperature higher than 26◦ C, annual precipitation about 10.000mm and annual potential evapotranspiration rate about 0.1. The difference between Holdridge predicted precipitation and the precipitation measured with TRMM are about 5.000mm in these places. Classification systems based on an annual average, do not stablish adaptation as a function of diurnal variability, for example, the difference between valley sides vegetation could not being determined. This kind of limitations, added to a validation procces and the auscence of a physic procces in the variable interaction, make the Holdridge Life Zones a very useful tool, but physically inconsistent for caracterice vegetation as a function of precipitation. The rain process is very complex, depend of mass and energy exchanges and is still a controversial topic in atmospheric modeling, as a biotic pump.

  5. Synaptic vesicle proteins and active zone plasticity

    Directory of Open Access Journals (Sweden)

    Robert J Kittel

    2016-04-01

    Full Text Available Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone. The complex molecular architecture of active zones mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of active zones vary significantly, even for a given connection. Thus, there appear to be distinct active zone states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the active zone.The protein-rich cytomatrix at the active zone (CAZ provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1 and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and active zone states, which has heretofore received little attention.

  6. Plan de Negocios: Networking Zone

    OpenAIRE

    Espol; Cárdenas Sáenz, Daniel Alejandro; Seminario Benalcázar, Ivette Dennisse

    2016-01-01

    Networking Zone se define coma una empresa que alquila espacios de trabajo totalmente amoblados y equipados, necesarios para los profesionales / emprendedores, ubicado en la ciudad de Guayaquil en un área de unos 800 metros cuadrados. Esta propuesta atiende la ausencia de espacios físicos amoblados para profesionales independientes, emprendedores, FreeLancer quienes buscan un lugar cómodo, accesible, con tecnología adecuada para cumplir sus necesidades de trabajo a un bajo costo, evtándole...

  7. Wood zone plate fishnet metalens

    Directory of Open Access Journals (Sweden)

    Orazbayev Bakhtiyar

    2015-01-01

    Full Text Available Fresnel-zone plate lenses provide focusing performance while having low profile. Unfortunately, they usually display higher reflection losses than conventional dielectric lenses. Here, we demonstrate a low-profile Wood zone plate metalens based on the fishnet metamaterial working in a near-zero regime with an equivalent refractive index less than unity (nf = 0.51. The metalens is made of alternating dielectric and fishnet metamaterial concentric rings. The use of fishnet metamaterial allows reducing the reflections from the lens, while maintaining low profile, low cost and ease of manufacturing. The lens is designed to work at the W-band of the millimeter-waves range with a focal length FL = 22.8 mm (7.5 λ0 aiming at antenna or radar system applications. The focusing performance of the lens along with its radiation characteristics in a lens antenna configuration have been studied numerically and confirmed experimentally, showing a gain improvement of ~2.5 dB with respect to a fishnet Soret metalens.

  8. Euphotic Zone Study moves forward

    Science.gov (United States)

    Denman, Kenneth

    The Global Ocean Euphotic Zone Study (GOEZS), a potential core program of the International Geosphere-Biosphere Programme (IGBP) being planned jointly with the Scientific Committee on Oceanic Research (SCOR), was recently given the go-ahead by IGBP's Scientific Committee to move on to the next level of developing its scientific program.The GOEZS program will focus on the coupled physical, biological, and chemical processes operating in the euphotic zone, which is the ocean surface layer where sufficient light penetrates for photosynthesis by phytoplankton to exceed their metabolic energy losses. The upper ocean is extremely important to understanding the atmosphereocean system because it mediates exchanges of heat, momentum, carbon dioxide, sulphur, and nitrogen between the atmosphere and the ocean interior. For the major greenhouse gas carbon dioxide for example, there is more carbon in the upper ocean than in the whole atmosphere. Essentially all carbon dioxide from the atmosphere that passes from the upper ocean to the ocean interior has been transformed chemically or biologically in the upper ocean. Moreover, the upper ocean is the site of all marine shipping and most recreation and industrial activity and contains the planktonic food chain and most fish stocks.

  9. Adult attachment styles

    Directory of Open Access Journals (Sweden)

    Maša Žvelc

    2007-01-01

    Full Text Available Theory of attachment primarily described early relationships between a child and his caretakers. In the last twenty years there is a growing interest in adult attachment research. Theories and research findings of adult attachment stem from two different methodological approaches. The first approach measures adult attachment through Adult Attachment Interview (AAI; Main, 1991 where the attachment is assessed through the narratives of adult people of their early child experiences with their primary caretakers. The second approach measures adult attachment with the help of self-evaluative questionnaires, developed by (a Hazan and Shaver (1987 who started this approach in the field of personality and social psychology, and (b Bartholomew and Horowitz (1991. Research shows that there is significant correlation between early and adult attachment style. Attachment styles are passed from generation to generation. Basic adult attachment styles are: securely attached, preoccupied, fearful-avoidant, dismissing-avoidant and disorganized. Previous research using Barholomew and Horowitz (1991 Relationship Questionnaire on 176 Slovenian students showed that 48% students are securely attached, 29% are fearful-avoidant, 10% are dismissing-avoidant, and 13% have preoccupied attachment style. Theory of attachment is very useful for understanding the behavior and subjective experiences of children and adults. It is applicable to different contexts (psychotherapy, counseling, education .... The paper proposes further research focused on integration of adult attachment styles and types of object relations measured by Test of object relations (Žvelc, 1998 and Pictorial test of Separation and Individuation (Žvelc, 2003.

  10. Crustal growth in subduction zones

    Science.gov (United States)

    Vogt, Katharina; Castro, Antonio; Gerya, Taras

    2015-04-01

    There is a broad interest in understanding the physical principles leading to arc magmatisim at active continental margins and different mechanisms have been proposed to account for the composition and evolution of the continental crust. It is widely accepted that water released from the subducting plate lowers the melting temperature of the overlying mantle allowing for "flux melting" of the hydrated mantle. However, relamination of subducted crustal material to the base of the continental crust has been recently suggested to account for the growth and composition of the continental crust. We use petrological-thermo-mechanical models of active subduction zones to demonstrate that subduction of crustal material to sublithospheric depth may result in the formation of a tectonic rock mélange composed of basalt, sediment and hydrated /serpentinized mantle. This rock mélange may evolve into a partially molten diapir at asthenospheric depth and rise through the mantle because of its intrinsic buoyancy prior to emplacement at crustal levels (relamination). This process can be episodic and long-lived, forming successive diapirs that represent multiple magma pulses. Recent laboratory experiments of Castro et al. (2013) have demonstrated that reactions between these crustal components (i.e. basalt and sediment) produce andesitic melt typical for rocks of the continental crust. However, melt derived from a composite diapir will inherit the geochemical characteristics of its source and show distinct temporal variations of radiogenic isotopes based on the proportions of basalt and sediment in the source (Vogt et al., 2013). Hence, partial melting of a composite diapir is expected to produce melt with a constant major element composition, but substantial changes in terms of radiogenic isotopes. However, crustal growth at active continental margins may also involve accretionary processes by which new material is added to the continental crust. Oceanic plateaus and other

  11. [Development and differentiation of the rat epididymis. I: ultrastructural aspects of the peritubular zone].

    Science.gov (United States)

    Francavilla, S; Santiemma, V; Francavilla, F; Moscardelli, S; Forcella, G; Fabbrini, A

    1979-07-15

    We investigated the ultrastructural aspects of the peritubular cells of epididymis and their development from birth to adult age. At birth the peritubular zone consisted of polygonal cells which did not differ from other interstitial cells. Cytoplasmic filaments were visible in the cells of the inner layer at day 6. From day 22 the peritubular cells reached the adult aspect. The peritubular cells in the rat epididymis had aspects similar to those of peritubular smooth muscle cells of rat testis, with a more precocious appearance of cytoplasmic filaments. This finding concurs with the observed precocious contractility of epididymis.

  12. Saltwater upconing zone of influence

    Science.gov (United States)

    Jakovovic, Danica; Werner, Adrian D.; de Louw, Perry G. B.; Post, Vincent E. A.; Morgan, Leanne K.

    2016-08-01

    In this study, we define and characterize the saltwater upconing zone of influence (SUZI). The SUZI is the region around a pumping well within which significant rise in the saltwater-freshwater interface occurs. While the zone of influence of a pumping well can be clearly defined in terms of hydraulics (e.g., drawdown), the SUZI has not been recognised and characterised, despite its importance for groundwater decision-making in coastal regions. We explore the SUZI under various conditions and compare common methods of investigation using both axisymmetric (1D and 2D vertical cross-section) and 3D simulations of saltwater upconing at the field scale, based on a combination of numerical and analytical approaches. The SUZI was found to be dependent on the relative magnitudes of pumping, regional flow, distance of the well from the coast, and position of the well above the interface, as expected. The three-dimensional coastal setting simulations revealed an asymmetric shape of the lateral extent of the SUZI, which is largest in the direction parallel to the coast. This occurs because the ocean and the inland extent of the seawater wedge limit the propagation of the SUZI perpendicular to the coast. Predictions of the SUZI using the Ghyben-Herzberg approximation, including cases where sloping interfaces occur (i.e., in contrast to the artificiality of horizontal interfaces used in axisymmetric approaches), provide reasonable first approximations of the SUZI. Numerical modelling of dispersive upconing in the 3D inclined interface case is influenced by practical limits to the model domain size and grid resolution. For example, the no-flow boundary condition at 1500 m from the pumping well elongates the SUZI in the direction parallel to the coast. This study extends previous concepts of well interference, which have previously been based on hydraulics only, by introducing the SUZI and characterising its extent, with consideration given to differences in commonly adopted

  13. Zone refining of cadmium and related characterization

    Indian Academy of Sciences (India)

    N R Munirathnam; D S Prasad; Ch Sudheer; J V Rao; T L Prakash

    2005-06-01

    We present the zone refining results of cadmium using horizontal resistive zone refiner under constant flow of moisture free hydrogen gas. The boron impurity in cadmium can be avoided using quartz (GE 214 grade) boat in lieu of high pure graphite boat. The analytical results using inductively coupled plasma optical emission spectrometry (ICPOES) show that majority of the impurities are less than the detection limits. Comparatively, zinc is the most difficult impurity element to remove in cadmium matrix by zone refining.

  14. Regulation of neurogenesis by neurotrophins during adulthood: expected and unexpected roles

    Directory of Open Access Journals (Sweden)

    Marçal eVilar

    2016-02-01

    Full Text Available The subventricular zone (SVZ of the anterolateral ventricle and the subgranular zone (SGZ of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin receptors in different scenarios, including both expected and unexpected functions.

  15. NOAA Average Annual Salinity (3-Zone)

    Data.gov (United States)

    California Department of Resources — The 3-Zone Average Annual Salinity Digital Geography is a digital spatial framework developed using geographic information system (GIS) technology. These salinity...

  16. Identification and culture of neural stem cells isolated from subventricular zone following injury caused by moderate lateral fluid percussion%液压性脑损伤后室下区神经干细胞的分离培养与鉴定

    Institute of Scientific and Technical Information of China (English)

    屈建强; 贺西京; 杨平林; 杨涛; 冯彦军

    2007-01-01

    目的 分离液压性脑损伤室下区巢蛋白(nestin)和胶质酸性纤维蛋白(GFAP)阳性(nestin+/GFAP+)共存细胞进行培养和诱导分化,观察其分裂、增殖和分化能力,以阐明损伤反应性星形胶质细胞增生过程中nestin+/GFAP+共存细胞是否具有神经干细胞特性.方法 用液压冲击法建立动物模型,分离损伤成年SD大鼠室下区nestin+/GFAP+共存细胞,制成单细胞悬液,培养和诱导分化,以免疫荧光化学方法对原代和传代培养形成的神经球以及原代和传代培养诱导分化的细胞进行鉴定.结果 结果显示培养及传代的细胞不断分裂增殖,可以形成悬浮生长nestin阳性的神经球;神经球诱导分化后可以分化为少突胶质细胞、神经元和星形胶质细胞.结论 成年大鼠液压性脑损伤后分离的室下区细胞具有自我更新能力和多向分化潜能,是中枢神经系统神经干细胞.

  17. Policy Change Implication Toward Integrated Wonorejo Zone as A Strategic Economic Development Zone

    Directory of Open Access Journals (Sweden)

    Akbar Pandu Dwinugraha

    2014-04-01

    Full Text Available Integrated Wonorejo Zone is one of the development zone in Lumajang Regency with significant goals to improve potensial condition in three aspect namely tourism, agriculture and SMEs. Based on RTRW in 2008-2028, which was established in 2008, the development strategy of this zone is change. Integrated Wonorejo Zone was mentioned as a Strategic Economic Development Zone. This research describe and analyse about how the implication of policy change toward Integrated Wonorejo Zone. This research using method of descriptive research with qualitative approach as well as analysis of data by John Seidel about QDA (qualitative data analysis. The result of this research explain that the policy change implication, from description, implementation and implication point of view did not give significant expectation. Key Words: Policy Change, Integrated Wonorejo Zone, Strategic Economic Development Zone.

  18. 76 FR 18393 - Safety Zones: Fireworks Displays in the Captain of the Port Columbia River Zone

    Science.gov (United States)

    2011-04-04

    ... determination based on the fact that this rule only changes the period during which the safety zone established...: The owners or operators of vessels wishing to transit the safety zone established by this rule....

  19. Communication practices of the Karen in Sheffield: Seeking to navigate their three zones of displacement

    OpenAIRE

    Green, Geff; Lockley, Eleanor

    2012-01-01

    This study investigates communication practices of a newly arrived Karen refugee community in the UK who, as well as establishing themselves in a strange country, seek to keep in touch, campaign politically and maintain identity collectively through communication and contact with their global diaspora. We look at the technologies, motivations and inhibiting factors applying to the communication by adult members of this community and construct the idea of three zones of displacement which help...

  20. Phenylketonuria (PKU in adults

    Directory of Open Access Journals (Sweden)

    Mercedes Martínez-Pardo

    2014-07-01

    Full Text Available Monitoring phenylketonuria adult patients is an important subject which has created considerable interest in specialized metabolic clinics. The aim of this paper is to present an overview of the experience with these patients in the Unit of Metabolic Diseases at the Hospital Ramon y Cajal; the use of sapropterin in adults is included.

  1. Authenticity in Adult Learning

    Science.gov (United States)

    Ashton, Sam

    2010-01-01

    This paper is concerned with the relationship between authenticity and adult learning and prompted by some studies in which adult "authentic learning" is a central concept. The implication revealed by them is that real-worldness of learning contexts, learning content and learning tasks is perceived as conferring authenticity on learning. Here,…

  2. Toward Transpersonal Adult Development

    Science.gov (United States)

    Boucouvalas, Marcie

    2016-01-01

    As a foundation for discussing transpersonal adult development, the author traces her trajectory, involvement in, and contribution to the modern transpersonal movement and her introduction of it to the adult learning literature, beginning during the early 1980s. Highlighted are the transpersonal domain and a differentiation between transpersonal…

  3. Adult learning in modernity

    DEFF Research Database (Denmark)

    Rasmussen, Palle

    2007-01-01

    The paper discusses the conditions for the growth of adult education in modern societies. It is argued that in modern adult life individual biographical reflection plays an increasing role, not only for educational and occupational choice but also in the process of identity formation and emotional...

  4. Participation in adult learning

    DEFF Research Database (Denmark)

    Desjardins, Richard

    2010-01-01

    This entry presents an internationally comparative overview of adult learning patterns. Emphasis is placed on who is participating in adult learning and the observed unequal chances to participate. The entry covers three overarching questions that are central to participation research: a) What...

  5. 78 FR 25410 - Safety Zone; Tall Ship Safety Zones; War of 1812 Bicentennial Commemoration, Great Lakes

    Science.gov (United States)

    2013-05-01

    ... in the Tall Ships Challenge Great Lakes 2013 and the War of 1812 Bicentennial Commemoration. These... Safety Zones; War of 1812 Bicentennial Commemoration, Great Lakes. (a) Locations. The following are... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Tall Ship Safety Zones; War of...

  6. Land use zones and land use patterns in the Atlantic Zone of Costa Rica

    NARCIS (Netherlands)

    Huising, E.J.

    1993-01-01

    This thesis describes an approach to land use inventory at the sub-regional scale in the Guacimo-Rio Jiménez-Siquirres (GRS) area in the Atlantic Zone of Costa Rica. Therefore, the concept of "land use zones" is introduced. The land use zone (LUZ) plays a central role in the definition of an observa

  7. 76 FR 18674 - Security Zones; Sector Southeastern New England Captain of the Port Zone

    Science.gov (United States)

    2011-04-05

    ... security zone encompassing all navigable waters around any cruise ship anchored or moored and 200-yard radius security zone encompassing all navigable waters around any cruise ship underway that is being... navigable waters within the Southeastern New England COTP zone. We propose to define a ``cruise ship'' as...

  8. Tracking adult stem cells.

    Science.gov (United States)

    Snippert, Hugo J; Clevers, Hans

    2011-02-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue--known as their niche--and thus, stem-cell studies should preferably be performed in a physiological context, rather than outside their natural environment. The mouse is an attractive model in which to study adult mammalian stem cells, as numerous experimental systems and genetic tools are available. In this review, we describe strategies commonly used to identify and functionally characterize adult stem cells in mice and discuss their potential, limitations and interpretations, as well as how they have informed our understanding of adult stem-cell biology. An accurate interpretation of physiologically relevant stem-cell assays is crucial to identify adult stem cells and elucidate how they self-renew and give rise to differentiated progeny.

  9. Adult and lifelong education

    DEFF Research Database (Denmark)

    Milana, Marcella; Holford, John; Mohorčič Špolar, Vida

    2014-01-01

    The contributions published in this special issue of Globalisation, Societies and Education draw from an international conference “Trans-nationalization of Educational Policy Making: Implications for Adult and Lifelong Learning”, held in Nottingham on 10-12 February 2012. The conference...... was organised by the Research Network on Policy Studies on Adult Education, established under the auspices of the European Society for the Research on the Education of Adults (ESREA). The aim of the conference was to explore how globalisation affects agency and policy processes in the area of adult and lifelong...... education, and the conditions or structures under which policy processes occur. The objective was to deepen understanding of how scientific inquiry – as a means of comprehending and interpreting current processes and their implications – can accompany and support contemporary developments in adult...

  10. Schizophrenia in older adults.

    Science.gov (United States)

    Collier, Elizabeth; Sorrell, Jeanne M

    2011-11-01

    Although the number of people older than 55 with schizophrenia is expected to double during the next 20 years, the research data on older adults with schizophrenia are limited. This appears to be because until the middle of the 20th century, it was assumed that mental illness in older adults was a part of the aging process and because older adults are often excluded from research investigations. Nursing research is needed to explore how people with schizophrenia learn to manage their problems as they age, as well as how those who are first diagnosed with schizophrenia in later life adapt to their illness. Mental health nurses need to be cautious in assigning premature labels to older adults with mental illness that may lead to unsubstantiated assumptions about levels of disability. Instead, nurses should realize individual potential regarding undiscovered strengths and should attempt to create interventions that recognize and foster personal development for older adults with schizophrenia.

  11. 46 CFR 76.27-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Zoning. 76.27-5 Section 76.27-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Electric Fire Detecting System, Details § 76.27-5 Zoning. (a) The fire detecting system shall be divided into...

  12. 46 CFR 76.30-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Zoning. 76.30-5 Section 76.30-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Pneumatic Fire Detecting System, Details § 76.30-5 Zoning. (a) The fire detecting system shall be divided into...

  13. Special Economic Zones Blaze New Trails

    Institute of Scientific and Technical Information of China (English)

    徐现祥; 陈小飞

    2008-01-01

    Special economic zones(SEZ) are starting points of incremental reform and opening-up in China. On the 30th anniversay of reform and opening-up,this article attempts to present a systematic review of the evolution,mechanism and performance of special economic zones as well as a pespective on SEZs’ furture development.

  14. CareZone adgangskontrol og demenshegn

    DEFF Research Database (Denmark)

    Hauberg, Nanna

    2015-01-01

    Rapporten er skrevet på baggrund af afprøvning af CareZone, adgangskontrol og demenshegn på Solgaven, Mariagerfjord kommune i perioden april 2014 til januar 2015.......Rapporten er skrevet på baggrund af afprøvning af CareZone, adgangskontrol og demenshegn på Solgaven, Mariagerfjord kommune i perioden april 2014 til januar 2015....

  15. A Novel Offset Fresnel Zone Plate Antenna

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A novel offset Fresnel Zone Plate reflector Antenna (FZPA) is proposed, the phase correcting zone of this FZPA is elliptic. Based on Physical Optics Method, the focusing characteristics of the reflector are analyzed. The comparison of this new FZPA with the circular FZPA and Mawzones FZPA is made.

  16. Treating tar sands formations with karsted zones

    Energy Technology Data Exchange (ETDEWEB)

    Vinegar, Harold J. (Bellaire, TX); Karanikas, John Michael (Houston, TX)

    2010-03-09

    Methods for treating a tar sands formation are described herein. The tar sands formation may have one or more karsted zones. Methods may include providing heat from one or more heaters to one or more karsted zones of the tar sands formation to mobilize fluids in the formation. At least some of the mobilized fluids may be produced from the formation.

  17. 46 CFR 76.25-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkling System, Details § 76.25-5 Zoning. (a) The automatic sprinkling system shall be divided into separate... more than 250 sprinkler heads. (c) The sprinkling zone may cover more than one deck, in which case,...

  18. Remote sensing applications for coastal zone management

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, L.V.G.

    stream_size 4 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_5.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_5.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

  19. Brief Introduction to Five Key Zones

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Liaoning Jinzhou Development Zone This zone includes Jinzhou Xihai Industrial Park and Huludao Beigang Industrial Park. The Jinzhou Xihai Industrial Park has a planned development area of 22.76 square km and a gross investment of 737 million yuan. It is featured in the sub-industries of heavy chemicals and petrochemicals that Include motor tool elements, medicine and production of containers.

  20. Louisiana Speaks Regional Plan Vision Special Economic Zones, UTM Zone 15N NAD83, Louisiana Recovery Authority (2007), [louisiana_speaks_vision_special_economic_zones

    Data.gov (United States)

    Louisiana Geographic Information Center — This GIS shapefile data illustrates special economic zones included in the Louisiana Speaks Regional Plan Vision. Special economic zones include existing national,...

  1. Earthcasting the future Critical Zone

    Directory of Open Access Journals (Sweden)

    Yves Goddéris

    2013-12-01

    Full Text Available Abstract As humans continue to impact the Critical Zone, we need to project how our environment will evolve into the future. To model such change requires the ability to simulate interactions among the lithosphere, pedosphere, hydrosphere, biosphere, and atmosphere — including the activities of humans. Such projections, which some have called earthcasts, must be made with mechanistic models that capture the important phenomena, as well as scenarios of human behavior. As an example, we present earthcasts of future weathering in the mid-continent of the USA into the next century of projected warming. Rates of sequestration of CO2 from the atmosphere due to weathering will change in the future as carbonate and silicate minerals are dissolved or precipitated in soil. The downward or upward advance of the carbonate reaction front in the soil is an analogue of the oceanic lysocline. Like the movement of the oceanic lysocline in response to oceanic acidification, this terrestrial lysocline will likely move due to fluxes of CO2 driven by human activity. Understanding this and other responses to perturbations will best be achieved using multiple models for earthcasting.

  2. UV Habitable Zones Further Constrain Possible Life

    Science.gov (United States)

    Kohler, Susanna

    2017-02-01

    Where should we search for life in the universe? Habitable zones are traditionallydetermined based on the possibility of liquid water existing on a planet but ultraviolet (UV) radiation also plays a key role.The UV Habitable ZoneSchematic showing how the traditional habitable zones location and width changes around different types of stars. The UV habitable zone also hasdifferent locations and widths depending on the mass and metallicity of the star. [NASA/Kepler Mission/Dana Berry]Besides the presence of liquid water, there are other things life may need to persist. For life as we know it, one important elementis moderate UV radiation: if a planet receives too little UV flux, many biological compounds cant be synthesized. If it receives too much, however, then terrestrial biological systems (e.g. DNA) can be damaged.To determinethe most likely place to findpersistent life, we should therefore look for the region where a stars traditional habitable zone, within which liquid water is possible, overlaps with its UV habitable zone, within which the UV flux is at the right level to support life.Relationship between the stellar mass and location of the boundaries of the traditional and UV habitable zones for a solar-metallicity star. din and dout denote inner and outer boundaries, respectively. ZAMS and TMS denote when the star joins and leaves the main sequence, respectively. The traditional and UV habitable zones overlap only for stars of 11.5 solar masses. [Adapted from Oishi and Kamaya 2016]Looking for OverlapIn a recent study, two scientists from the National Defense Academy of Japan, Midori Oishi and Hideyuki Kamaya, explored howthe location of this UV habitable zone and that of its overlap with the traditional habitable zone might be affected by a stars mass and metallicity.Oishi and Kamaya developed a simple evolutional model of the UV habitable zone in stars in the mass range of 0.084 solar masses with metallicities of roughly solar metallicity (Z=0.02), a

  3. Trading Zones in Early Modern Europe.

    Science.gov (United States)

    Long, Pamela O

    2015-12-01

    This essay adopts the concept of trading zones first developed for the history of science by Peter Galison and redefines it for the early modern period. The term "trading zones" is used to mean arenas in which substantive and reciprocal communication occurred between individuals who were artisanally trained and learned (university-trained) individuals. Such trading zones proliferated in the sixteenth century. They tended to arise in certain kinds of places and not in others, but their existence must be determined empirically. The author's work on trading zones differs from the ideas of Edgar Zilsel, who emphasized the influence of artisans on the scientific revolution. In contrast, in this essay, the mutual influence of artisans and the learned on each other is stressed, and translation is used as a modality that was important to communication within trading zones.

  4. Adults with Congenital Heart Defects

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Web Booklet: Adults With Congenital Heart Defects Updated:Apr 24,2014 From the Committee on ... below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: Adults with Congenital Heart Defects Introduction: ...

  5. College-Age & Young Adults

    Science.gov (United States)

    ... Home » Related Topics » College-Age & Young Adults College-Age & Young Adults Email Facebook Twitter Daily marijuana use ... the country. Drug and Alcohol Use in College-Age Adults in 2015 Infographic View Full Infographic Monitoring ...

  6. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    José J Rodríguez

    Full Text Available It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ of the dentate gyrus (DG of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD harbouring three mutant genes (beta-amyloid precursor protein, presenilin-1 and tau and their respective non-transgenic (non-Tg controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3, and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63% with an almost inexistent rate at 12 months (88% decrease compared to controls. This reduction in neurogenesis was directly associated with the presence of beta-amyloid plaques and an increase in the number of beta-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These

  7. Formulating a coastal zone health metric for landuse impact management in urban coastal zones.

    Science.gov (United States)

    Anilkumar, P P; Varghese, Koshy; Ganesh, L S

    2010-11-01

    The need for ICZM arises often due to inadequate or inappropriate landuse planning practices and policies, especially in urban coastal zones which are more complex due to the larger number of components, their critical dimensions, attributes and interactions. A survey of literature shows that there is no holistic metric for assessing the impacts of landuse planning on the health of a coastal zone. Thus there is a need to define such a metric. The proposed metric, CHI (Coastal zone Health Indicator), developed on the basis of coastal system sustainability, attempts to gauge the health status of any coastal zone. It is formulated and modeled through an expert survey and pertains to the characteristic components of coastal zones, their critical dimensions, and relevant attributes. The proposed metric is applied to two urban coastal zones and validated. It can be used for more coast friendly and sustainable landuse planning/masterplan preparation and thereby for the better management of landuse impacts on coastal zones.

  8. TUM Critical Zone Observatory, Germany

    Science.gov (United States)

    Völkel, Jörg; Eden, Marie

    2014-05-01

    Founded 2011 the TUM Critical Zone Observatory run by the Technische Universität München and partners abroad is the first CZO within Germany. TUM CZO is both, a scientific as well as an education project. It is a watershed based observatory, but moving behind this focus. In fact, two mountainous areas are integrated: (1) The Ammer Catchment area as an alpine and pre alpine research area in the northern limestone Alps and forelands south of Munich; (2) the Otter Creek Catchment in the Bavarian Forest with a crystalline setting (Granite, Gneiss) as a mid mountainous area near Regensburg; and partly the mountainous Bavarian Forest National Park. The Ammer Catchment is a high energy system as well as a sensitive climate system with past glacial elements. The lithology shows mostly carbonates from Tertiary and Mesozoic times (e.g. Flysch). Source-to-sink processes are characteristic for the Ammer Catchment down to the last glacial Ammer Lake as the regional erosion and deposition base. The consideration of distal depositional environments, the integration of upstream and downstream landscape effects are characteristic for the Ammer Catchment as well. Long term datasets exist in many regards. The Otter Creek catchment area is developed in a granitic environment, rich in saprolites. As a mid mountainous catchment the energy system is facing lower stage. Hence, it is ideal comparing both of them. Both TUM CZO Catchments: The selected catchments capture the depositional environment. Both catchment areas include historical impacts and rapid land use change. Crosscutting themes across both sites are inbuilt. Questions of ability to capture such gradients along climosequence, chronosequence, anthroposequence are essential.

  9. A Volcanic Hydrogen Habitable Zone

    Science.gov (United States)

    Ramirez, Ramses M.; Kaltenegger, Lisa

    2017-03-01

    The classical habitable zone (HZ) is the circular region around a star in which liquid water could exist on the surface of a rocky planet. The outer edge of the traditional N2–CO2–H2O HZ extends out to nearly ∼1.7 au in our solar system, beyond which condensation and scattering by CO2 outstrips its greenhouse capacity. Here, we show that volcanic outgassing of atmospheric H2 can extend the outer edge of the HZ to ∼2.4 au in our solar system. This wider volcanic-hydrogen HZ (N2–CO2–H2O–H2) can be sustained as long as volcanic H2 output offsets its escape from the top of the atmosphere. We use a single-column radiative-convective climate model to compute the HZ limits of this volcanic hydrogen HZ for hydrogen concentrations between 1% and 50%, assuming diffusion-limited atmospheric escape. At a hydrogen concentration of 50%, the effective stellar flux required to support the outer edge decreases by ∼35%–60% for M–A stars. The corresponding orbital distances increase by ∼30%–60%. The inner edge of this HZ only moves out ∼0.1%–4% relative to the classical HZ because H2 warming is reduced in dense H2O atmospheres. The atmospheric scale heights of such volcanic H2 atmospheres near the outer edge of the HZ also increase, facilitating remote detection of atmospheric signatures.

  10. English in Adult Education

    OpenAIRE

    Ostrowska, Katarzyna, 1985-

    2014-01-01

    The study was conducted in order to investigate the effectiveness of a specialized program to meet the needs of adults who have diverse English skills and use English as a Lingua Franca. The program was developed for Menntastoðir, an adult education program in Reykjanesbær. Menntastoðir is an adult education institution that provides opportunities for improving adults’ knowledge and competences. The purpose of the study is to map out the type and amount of English exposure among Menntastoðir ...

  11. Radiation danger of exclusion zone objects

    Energy Technology Data Exchange (ETDEWEB)

    Kholosha, V.I.; Proskura, N.I.; Ivanov, Yu.A.; Kazakov, S.V.; Arkhipov, A.N. [Ministry of Ukraine of Emergencies and Affairs of Population Protection from the Consequences of Chornobyl Catastrophe (Ukraine)

    2001-03-01

    The analysis of radiation danger of the Exclusion Zone objects was made. Here, the Zone is defined as the territory from which the population has been evacuated in 1986 owing to the Chernobyl accident and possible outflow of the contaminated substances out of the borders is potentially dangerous to the Ukraine. In the present work were analyzed such problems as sources of radiation danger in the Zone, ways of radionuclide migration out of the borders of the Zone in normal and emergency situations, the non-radiation (ecological) danger factors of the Zone objects, doses (individual and collective) from various sources and on separate ways of their formation, and the characteristics of radiation danger of the Zone objects. The conclusions are: (1) Radionuclide flows both from technologic and natural sources exceed those from Shelter objects, (2) Under emergency conditions, radionuclide flows and doze loading remain comparable with those from emergency sources, (3) To solve some management tasks in radiation situation, the basic works on the Shelter objects should be oriented to decrease probability of emergency occurrence and to reduce radiation influence (prevention wash-outs during high waters, fire-prevention measures in forests and strengthening of the control behind non-authorized use of objects in the Zone). (S. Ohno)

  12. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Willem Kamphuis

    Full Text Available Glial fibrillary acidic protein (GFAP is the main astrocytic intermediate filament (IF. GFAP splice isoforms show differential expression patterns in the human brain. GFAPδ is preferentially expressed by neurogenic astrocytes in the subventricular zone (SVZ, whereas GFAP(+1 is found in a subset of astrocytes throughout the brain. In addition, the expression of these isoforms in human brain material of epilepsy, Alzheimer and glioma patients has been reported. Here, for the first time, we present a comprehensive study of GFAP isoform expression in both wild-type and Alzheimer Disease (AD mouse models. In cortex, cerebellum, and striatum of wild-type mice, transcripts for Gfap-α, Gfap-β, Gfap-γ, Gfap-δ, Gfap-κ, and a newly identified isoform Gfap-ζ, were detected. Their relative expression levels were similar in all regions studied. GFAPα showed a widespread expression whilst GFAPδ distribution was prominent in the SVZ, rostral migratory stream (RMS, neurogenic astrocytes of the subgranular zone (SGZ, and subpial astrocytes. In contrast to the human SVZ, we could not establish an unambiguous GFAPδ localization in proliferating cells of the mouse SVZ. In APPswePS1dE9 and 3xTgAD mice, plaque-associated reactive astrocytes had increased transcript levels of all detectable GFAP isoforms and low levels of a new GFAP isoform, Gfap-ΔEx7. Reactive astrocytes in AD mice showed enhanced GFAPα and GFAPδ immunolabeling, less frequently increased vimentin and nestin, but no GFAPκ or GFAP(+1 staining. In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches. Furthermore, differential GFAP isoform expression is not linked with aging or reactive gliosis. This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain.

  13. Shear zone junctions: Of zippers and freeways

    Science.gov (United States)

    Passchier, Cees W.; Platt, John P.

    2017-02-01

    Ductile shear zones are commonly treated as straight high-strain domains with uniform shear sense and characteristic curved foliation trails, bounded by non-deforming wall rock. Many shear zones, however, are branched, and if movement on such branches is contemporaneous, the resulting shape can be complicated and lead to unusual shear sense arrangement and foliation geometries in the wall rock. For Y-shaped shear zone triple junctions with three joining branches and transport direction at a high angle to the branchline, only eight basic types of junction are thought to be stable and to produce significant displacement. The simplest type, called freeway junctions, have similar shear sense in all three branches. The other types show joining or separating behaviour of shear zone branches similar to the action of a zipper. Such junctions may have shear zone branches that join to form a single branch (closing zipper junction), or a single shear zone that splits to form two branches, (opening zipper junction). All categories of shear zone junctions show characteristic foliation patterns and deflection of markers in the wall rock. Closing zipper junctions are unusual, since they form a non-active zone with opposite deflection of foliations in the wall rock known as an extraction fault or wake. Shear zipper junctions can form domains of overprinting shear sense along their flanks. A small and large field example are given from NE Spain and Eastern Anatolia. The geometry of more complex, 3D shear zone junctions with slip parallel and oblique to the branchline is briefly discussed.

  14. Knowledge-based flow field zoning

    Science.gov (United States)

    Andrews, Alison E.

    1988-01-01

    Automation flow field zoning in two dimensions is an important step towards easing the three-dimensional grid generation bottleneck in computational fluid dynamics. A knowledge based approach works well, but certain aspects of flow field zoning make the use of such an approach challenging. A knowledge based flow field zoner, called EZGrid, was implemented and tested on representative two-dimensional aerodynamic configurations. Results are shown which illustrate the way in which EZGrid incorporates the effects of physics, shape description, position, and user bias in a flow field zoning.

  15. New national seismic zoning map of China

    Institute of Scientific and Technical Information of China (English)

    高孟潭

    2003-01-01

    A new set of seismic zoning maps were published in August 1,200l. It includes two maps, one is the seismic zon-ing map of peak acceleration, and the other is the zoning map of the characteristic period of the response spectrum.The exceeding probability of the map is 10% within 50 years. The scale of the map is 1:4 000 000. These mapsserve as the national standard. The background of this project, technical approach and key scientific measures, thebasic feature and the application of the maps are introduced in this paper.

  16. Flow and transport in Riparian Zones

    DEFF Research Database (Denmark)

    Jensen, Jannick Kolbjørn

    of riparian zones are extended by accounting for the effect of flooding and a key result is that flooding enhances nitrate removal given the right hydrogeological characteristics. Moreover the re-established riparian zones were characterized to understand the effects of flooding on subsurface hydrological......) and easurements of discharge to the river by seepage meter and river bed temperatures. The numerical model was used to simulate how observed dynamic seasonal flooding affects groundwater flow paths, residence times, and formation of zones with flow stagnation, all of which are key aspects in evaluating...

  17. Immunization Schedules for Adults

    Science.gov (United States)

    ... Everyone: Easy-to-read Schedules Infants and Children Preteens and Teens Adults Display Immunization Schedules and Quiz ... file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file ...

  18. Pneumonia - adults - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000017.htm Pneumonia in adults - discharge To use the sharing features on this page, please enable JavaScript. You have pneumonia, which is an infection in your lungs. In ...

  19. Older Adults and Depression

    Science.gov (United States)

    ... find more information? Reprints Share Older Adults and Depression Download PDF Download ePub Order a free hardcopy ... depression need treatment to feel better. Types of Depression There are several types of depression. The most ...

  20. Information for Adults

    Science.gov (United States)

    ... occurrence. Well, so much for statistics! Life seemed unjust again! I had not chosen this! Through much ... to the cleft may help. Facial Appearance Surgical Considerations in the Adult Patient Input and Surgeon Selection ...

  1. Older Adults and Alcohol

    Science.gov (United States)

    ... Problems Certain health problems are common in older adults. Heavy drinking can make these problems worse, including: Diabetes High blood pressure Congestive heart failure Liver problems Osteoporosis Memory problems Mood disorders Bad Interactions with Medications ...

  2. Young Adult Books.

    Science.gov (United States)

    Epstein, Connie C.

    1987-01-01

    Considers the similarities between science fiction writing and young adult literature, and points out that several well-known authors, such as Robert Heinlein and Jane Yolen, write in both genres. (NKA)

  3. [Advanced resuscitation of adults

    DEFF Research Database (Denmark)

    Lippert, F.K.; Lauritsen, T.L.; Torp-Pedersen, C.

    2008-01-01

    International and European Resuscitation Council (ERC) Guidelines for Resuscitation 2005 implicate major changes in resuscitation, including new universal treatment algorithms. This brief summary of Guidelines 2005 for advanced resuscitation of adult cardiac arrest victims is based upon the ERC...

  4. Urinary tract infection - adults

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000521.htm Urinary tract infection - adults To use the sharing features on this page, please enable JavaScript. A urinary tract infection, or UTI, is an infection of the urinary ...

  5. Mosquito, adult (image)

    Science.gov (United States)

    This illustration shows an adult southern house mosquito. This mosquito feeds on blood and is the carrier of many diseases, such as encephalitis, West Nile, dengue fever, yellow fever, and others. ( ...

  6. Motivation and Adult Education.

    Science.gov (United States)

    Taylor, J. Rodney

    1982-01-01

    The author reviews theories of human motivation: Lewin's force field analysis, Skinner's operant reinforcement theory, and Maslow's hierarchy of needs. He then extracts the implications of these theories for adult learning. SK)

  7. NOHSS Adult Indicators

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1999, 2002-2014 (even years). Data from BRFSS for indicators of adult oral health for 1999 and even years from 2002 through 2014. National estimates are represented...

  8. NOHSS Adult Indicators

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2012-2014 (even years). Data from BRFSS for indicators of adult oral health for even years from 2012 through 2014. National estimates are represented by the median...

  9. Falls and Older Adults

    Science.gov (United States)

    ... version of this page please turn Javascript on. Falls and Older Adults About Falls Risk Increases With Age Many people have a ... problems -- rises with age. Click for more information Falls Lead to Fractures, Trauma Each year, more than ...

  10. About BMI for Adults

    Science.gov (United States)

    ... Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs About Adult BMI ... Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Language: English Español ( ...

  11. Speech impairment (adult)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  12. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  13. Adult onset tic disorders

    OpenAIRE

    Chouinard, S; Ford, B.

    2000-01-01

    BACKGROUND—Tic disorders presenting during adulthood have infrequently been described in the medical literature. Most reports depict adult onset secondary tic disorders caused by trauma, encephalitis, and other acquired conditions. Only rare reports describe idiopathic adult onset tic disorders, and most of these cases represent recurrent childhood tic disorders.
OBJECTIVE—To describe a large series of patients with tic disorders presenting during adulthood, to compare cl...

  14. Adult extracardiac rhabdomyoma

    DEFF Research Database (Denmark)

    Bjørndal Sørensen, Kristine; Godballe, Christian; Ostergaard, Birthe;

    2006-01-01

    BACKGROUND: We present two cases of adult rhabdomyoma in the parapharyngeal space. They are rare benign tumors with a characteristic histologic appearance. METHODS: The tumors were studied by light and immunohistochemical analysis using stains characteristic of striated muscle fibers. RESULTS...... slight proliferation with incipient differentiation in an otherwise mature tumor. CONCLUSION: The head and neck area harbors 90% of adult rhabdomyomas and should be considered in a differential diagnosis in this region. Immunohistochemistry confirms that the tumors are almost totally mature neoplasms...

  15. Adult educators' core competences

    Science.gov (United States)

    Wahlgren, Bjarne

    2016-06-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or "core" requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students' prior learning into account; (3) supporting a learning environment; and (4) the adult educator's reflection on his or her own performance. At the end of his analysis of different competence profiles, the author notes that adult educators' ability to train adult learners in a way which then enables them to apply and use what they have learned in practice (thus performing knowledge transfer) still seems to be overlooked.

  16. Proliferation zones in the axolotl brain and regeneration of the telencephalon

    Directory of Open Access Journals (Sweden)

    Maden Malcolm

    2013-01-01

    Full Text Available Abstract Background Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion There is a continual generation of neuronal cells from neural progenitor cells

  17. Global challenges in integrated coastal zone management

    DEFF Research Database (Denmark)

    integration of data and information in policy and management, combining expertise from nature and social science, to reach a balanced and sustainable development of the coastal zone. This important book comprises the proceedings of The International Symposium on Integrated Coastal Zone Management, which took......Growing pressure from increasingly diverse human activities coupled with climate change impacts threaten the functional integrity of coastal ecosystems around the globe. A multi-disciplinary approach towards understanding drivers, pressures and impacts in the coastal zone requires effective....../mitigation to change in coastal systems Coastal governance Linking science and management Comprising a huge wealth of information, this timely and well-edited volume is essential reading for all those involved in coastal zone management around the globe. All libraries in research establishments and universities where...

  18. White Light Photorefractive Phase Zone Plates

    Institute of Scientific and Technical Information of China (English)

    GAO Yuan-Mei; LIU Si-Min

    2008-01-01

    Incoherent white light from an incandescent source is employed to Fabricate volume phase zone plates in LiNbO3:Fe,for the first time to our knowledge,which can guide and modulate the input white light or laser light.The diffractive efficiency of the white light volume phase zone plates fabricated can reach as high as 12%.In addition,we test the volume phase zone plates by a probe beam and find that the volume phase zone plate is present in the direction perpendicular to the c-axis and absent in the direction parallel to the c-axis.This directly proves the existence of photovoltalc photorefractive anisotropy of white light.

  19. Strategic metal deposits of the Arctic Zone

    Science.gov (United States)

    Bortnikov, N. S.; Lobanov, K. V.; Volkov, A. V.; Galyamov, A. L.; Vikent'ev, I. V.; Tarasov, N. N.; Distler, V. V.; Lalomov, A. V.; Aristov, V. V.; Murashov, K. Yu.; Chizhova, I. A.; Chefranov, R. M.

    2015-11-01

    Mineral commodities rank high in the economies of Arctic countries, and the status of mineral resources and the dynamics of their development are of great importance. The growing tendency to develop strategic metal resources in the Circumarctic Zone is outlined in a global perspective. The Russian Arctic Zone is the leading purveyor of these metals to domestic and foreign markets. The comparative analysis of tendencies in development of strategic metal resources of the Arctic Zone in Russia and other countries is crucial for the elaboration of trends of geological exploration and research engineering. This paper provides insight into the development of Arctic strategic metal resources in global perspective. It is shown that the mineral resource potential of the Arctic circumpolar metallogenic belt is primarily controlled by large and unique deposits of nonferrous, noble, and rare metals. The prospective types of economic strategic metal deposits in the Russian Arctic Zone are shown.

  20. EPA Region 1 No Discharge Zones

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset details No Discharge Zones (NDZ) for New England. Boaters may not discharge waste into these areas. Boundaries were determined mostly by Federal...

  1. WVSAMB Color Digital Orthophotos North Zone

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Digital color orthophotography of the State of West Virginia (West Virginia State Plane Coordinate System North Zone). The W.V. state plane system has two...

  2. Schools K-12 - School Board Zones

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This dataset contains polygons and attributes which represent the School District Board Zones for the Public School Districts in the State of Arkansas. It includes...

  3. VT New Market Tax Credit - Hot Zones

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The EconOther_NMTC layer delineates New Market Tax Credit (NMTC) "hot zones" and qualified counties and census tracts. This dataset is designed to...

  4. Spatial distribution of juvenile and adult stages of limnetic Cladocera in relation to selected environmental factors

    Directory of Open Access Journals (Sweden)

    Małgorzata Adamczuk

    2012-01-01

    Full Text Available Environmental factors have a varied impact on the development of juvenile and adult Cladocera, depending on their different physiological conditions and body size. The values of these factors alter spatially and temporarily, thus implying that they play a role in the spatial distribution of the pre-reproductive and potentially reproductive stages of cladocerans. The aim of the study was to determine seasonal and spatial variations in the distribution of juvenile and adult individuals of limnetic Cladocera in relation to selected physicochemical factors (temperature, conductivity, pH, concentration of dissolved oxygen, total organic carbon, total suspended solids and fish predation pressure (measured by Chesson’s coefficient λ in deep Lake Piaseczno (eastern Poland. Adult Cladocera displayed spatial distribution related to fish predation pressure. The species selectively eaten, B. coregoni and D. longispina, and non-selectively eaten, D. cucullata, selected the pelagic zone to exist, whereas those avoided by fish, D. brachyurum and B. longirostris, were evenly distributed in the littoral and pelagic zone. Juvenile cladocerans were strongly impacted by physico-chemical factors. Juvenile Daphnia, Diaphanosoma and B. longirostris showed preferences to biotic zones similar to the adults but differed in their habitat choices. Juvenile and adult stages of B. coregoni differed in their distribution, indicating that adult individuals impacted by high predation pressure alternatively modified their habitat selection. Principal component analysis (PCA ordination showed a seasonal tendency for the spatial segregation of the cladocerans, suggesting that possible competitive interactions between the studied cladocerans may also influence their distribution patterns.

  5. Treating nahcolite containing formations and saline zones

    Energy Technology Data Exchange (ETDEWEB)

    Vinegar, Harold J

    2013-06-11

    A method for treating a nahcolite containing subsurface formation includes removing water from a saline zone in or near the formation. The removed water is heated using a steam and electricity cogeneration facility. The heated water is provided to the nahcolite containing formation. A fluid is produced from the nahcolite containing formation. The fluid includes at least some dissolved nahcolite. At least some of the fluid is provided to the saline zone.

  6. Zone heated diesel particulate filter electrical connection

    Science.gov (United States)

    Gonze, Eugene V.; Paratore, Jr., Michael J.

    2010-03-30

    An electrical connection system for a particulate filter is provided. The system includes: a particulate filter (PF) disposed within an outer shell wherein the PF is segmented into a plurality of heating zones; an outer mat disposed between the particulate filter and the outer shell; an electrical connector coupled to the outer shell of the PF; and a plurality of printed circuit connections that extend along the outer surface of the PF from the electrical connector to the plurality of heating zones.

  7. Euro zone and its monetary policy

    OpenAIRE

    Dorel Dumitru CHIRIŢESCU; Andreea ANDRAŞIU

    2010-01-01

    In this article I have tried to make a short presentation of the Euro Zone and it’s monetary policy. At the present moment the Euro Zone has 16 countries that have adopted the Euro as a national currency and also 4 small countries that have monetary agreements with their neighbours. The monetary policy represents all the regulations of the money supply and interest rates adopted by the European Central Bank in order to control the inflation rate and to stabilize ...

  8. Clinical crown lengthening in the esthetic zone.

    Science.gov (United States)

    Camargo, Paulo M; Melnick, Philip R; Camargo, Luciano M

    2007-07-01

    Periodontal surgical procedures consisting of gingival flaps and osseous recontouring are indicated for crown lengthening of several contiguous teeth in the esthetic zone; both in cases where restorations are required and in cases where no restorations are planned, such as in patients with excessive gingival display due to altered passive eruption. Forced tooth eruption via orthodontic extrusion is the technique of choice when clinical crown lengthening is necessary on isolated teeth in the esthetic zone.

  9. MANIFESTATION OF FAULT ZONES IN GEOPHYSICAL FIELDS

    Directory of Open Access Journals (Sweden)

    A. A. Spivak

    2015-09-01

    Full Text Available Geophysical fields influenced by tectonics faults were observed, and instrumental observation results are analysed in the article. It is shown that fault zones are characterized by geophysical fields that are more variable than those in midmost segments of crustal blocks, more intense responses to weak external impacts such as lunar and solar tides and atmospheric pressure variations, and intensive relaxation. Transformation of energy between geophysical fields varying in origin takes place mainly in the fault zones.

  10. Zone conditioning in a California foothill house

    Energy Technology Data Exchange (ETDEWEB)

    Jump, D.; Modera, M.

    1993-12-01

    The principal focus of the reported research is the performance of the installed zoned air distribution system in a house located in the foothills northeast of Sacramento California. The 297 m{sup 2} two story house contained a central air conditioner and an air distribution system with four dampered supply duct legs. The air conditioning system included a two speed fan and two speed compressor, with the air handler placed inside a closet and almost all the ducts located inside the building envelope. The uninsulated sheet metal ducts ran inside a space between stories and in interior walls. The performance parameters examined included: (1) duct leakage, (2) duct conduction, (3) zoning performance and (4) equipment efficiency impacts. In conclusion, two major points were made concerning the test house. The first was that substantial energy benefits were obtained by placing the ducts inside the conditioned space. The second was that the energy benefits from zoning the house were not realized, primarily due to thermal stratification and the open floor plan in the house. Secondary impacts lowering zoning performance were the k& of return duct dampers and leakage and conduction losses in the air distribution system. Utility programs or building standards promoting zoning as a means of conserving energy or reducing peak power demand should be aware of the many potential pitfalls that can arise with zone conditioning, particularly with dampered air distribution systems.

  11. Ephrin-B3 decreases the survival of adult rat spinal cord-derived neural stem/progenitor cells in vitro and after transplantation into the injured rat spinal cord.

    Science.gov (United States)

    Fan, Xin Yan Susan; Mothe, Andrea J; Tator, Charles H

    2013-02-01

    Although transplantation of neural stem/progenitor cells (NSPC) encourages regeneration and repair after spinal cord injury (SCI), the survival of transplanted NSPC is limited. Ephrin-B3 has been shown to reduce the death of endogenous NSPC in the subventricular zone of the mouse brain without inducing uncontrolled proliferation. Due to similarities in the environment of the brain and spinal cord, we hypothesized that ephrin-B3 might reduce the death of both transplanted and endogenous spinal cord-derived NSPC. Both normal and injured (26 g clip compression) spinal cords were examined. Ephrin-B3-Fc was tested, and Fc fragments and phosphate-buffered saline (PBS) were used as controls. We found that EphA4 receptors were expressed by spinal cord-derived NSPC and expressed in the normal and injured rat spinal cord (higher expression in the latter). In vitro, ephrin-B3-Fc did not significantly reduce the survival of NSPC except at 1 μg/mL (Pinjured spinal cord compared with the infusion of PBS (Pinjured spinal cord, the infusion of either ephrin-B3-Fc or Fc fragments alone caused a 20-fold reduction in the survival of transplanted NSPC (P<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

  12. Standardized precipitation index zones for Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Giddings, L.; Soto, M. [Instituto de Ecologia, A.C., Xalapa, Veracruz (Mexico); Rutherford, B.M.; Maarouf, A. [Faculty of Environmental Studies, York University, Toronto, Ontario (Canada)

    2005-01-01

    Precipitation zone systems exists for Mexico based on seasonality, quantity of precipitation, climates and geographical divisions, but none are convenient for the study of the relation of precipitation with phenomena such as El nino. An empirical set of seven exclusively Mexican and six shared zones was derived from three series of Standardized Precipitation Index (SPI) images, from 1940 through 1989: a whole year series (SPI-12) of 582 monthly images, a six month series (SPI-6) of 50 images for winter months (November through April), and a six month series (SPI-6) of 50 images for summer months (May through October). By examination of principal component and unsupervised classification images, it was found that all three series had similar zones. A set of basic training fields chosen from the principal component images was used to classify all three series. The resulting thirteen zones, presented in this article, were found to be approximately similar, varying principally at zones edges. A set of simple zones defined by just a few vertices can be used for practical operations. In general the SPI zones are homogeneous, with almost no mixture of zones and few outliers of one zone in the area of others. They are compared with a previously published map of climatic regions. Potential applications for SPI zones are discussed. [Spanish] Existen varios sistemas de zonificacion de Mexico basados en la estacionalidad, cantidad de precipitacion, climas y divisiones geograficas, pero ninguno es conveniente para el estudio de la relacion de la precipitacion con fenomenos tales como El Nino. En este trabajo se presenta un conjunto de siete zonas empiricas exclusivamente mexicanas y seis compartidas, derivadas de tres series de imagenes de SPI (Indice Estandarizado de la Precipitacion), desde 1940 a 1989: una serie de 582 imagenes mensuales (SPI-12), una series de 50 imagenes (SPI-6) de meses de invierno (noviembre a abril), y otra de 50 imagenes (SPI-6) de meses de verano

  13. Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xuefeng Jing

    Full Text Available Cells of the neural stem cell lineage in the adult subventricular zone (SVZ respond to brain insult by increasing their numbers and migrating through the rostral migratory stream. However, in most areas of the brain other than the SVZ and the subgranular zone of the dentate gyrus, such a regenerative response is extremely weak. Even these two neurogenic regions do not show extensive regenerative responses to repair tissue damage, suggesting the presence of an intrinsic inhibitory microenvironment (niche for stem cells. In the present study, we assessed the effects of injection of clustered ephrin-A1-Fc into the lateral ventricle of rats with unilateral nigrostriatal dopamine depletion. Ephrin-A1-Fc clustered by anti-IgG(Fc antibody was injected stereotaxically into the ipsilateral lateral ventricle of rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine, and histologic analysis and behavioral tests were performed. Clustered ephrin-A1-Fc transformed the subventricular niche, increasing bromodeoxyuridine-positive cells in the subventricular area, and the cells then migrated to the striatum and differentiated to dopaminergic neurons and astrocytes. In addition, clustered ephrin-A1-Fc enhanced angiogenesis in the striatum on the injected side. Along with histologic improvements, behavioral derangement improved dramatically. These findings indicate that the subventricular niche possesses a mechanism for regulating both stem cell and angiogenic responses via an EphA-mediated signal. We conclude that activation of EphA receptor-mediated signaling by clustered ephrin-A1-Fc from within the lateral ventricle could potentially be utilized in the treatment of neurodegenerative diseases such as Parkinson's disease.

  14. Hypertension in young adults.

    Science.gov (United States)

    De Venecia, Toni; Lu, Marvin; Figueredo, Vincent M

    2016-01-01

    Hypertension remains a major societal problem affecting 76 million, or approximately one third, of US adults. While more prevalent in the older population, an increasing incidence in the younger population, including athletes, is being observed. Active individuals, like the young and athletes, are viewed as free of diseases such as hypertension. However, the increased prevalence of traditional risk factors in the young, including obesity, diabetes mellitus, and renal disease, increase the risk of developing hypertension in younger adults. Psychosocial factors may also be contributing factors to the increasing incidence of hypertension in the younger population. Increased left ventricular wall thickness and mass are increasingly found in young adults on routine echocardiograms and predict future cardiovascular events. This increasing incidence of hypertension in the young calls for early surveillance and prompt treatment to prevent future cardiac events. In this review we present the current epidemiological data, potential mechanisms, clinical implications, and treatment of hypertension in young patients and athletes.

  15. Electroporation of adult zebrafish.

    Science.gov (United States)

    Rao, N Madhusudhana; Rambabu, K Murali; Rao, S Harinarayana

    2008-01-01

    We generated transient transgenic zebrafish by applying electrical pulses subsequent to injection of DNA into muscle tissue of 3-6-month old adult zebrafish. Electroporation parameters, such as number of pulses, voltage, and amount of plasmid DNA, were optimized and found that 6 pulses of 40 V/cm at 15 mug/fish increased the luciferase expression by 10-fold compared with those in controls. By measuring the expression of luciferase, in vivo by electroporation in adult zebrafish and in vitro using fish cell line (Xiphophorus xiphidium A2 cells), the strength of three promoters (CMV, human EF-1alpha, and Xenopus EF-1alpha) was compared. Subsequent to electroporation after injecting DNA in the mid region of zebrafish, expression of green fluorescent protein was found far away from the site of injection in the head and the tail sections. Thus, electroporation in adult zebrafish provides a rapid way of testing the behavior of gene sequences in the whole organism.

  16. En echelon knolls in the Nosappu Fracture Zone, NW Pacific: A possible leaky transform fault zone

    Science.gov (United States)

    Ogawa, Y.; Hirano, N.; Shipboard Scientific Party Kr03-07, .

    2003-12-01

    During JAMSTEC R/V KAIREI cruise KR03-07, we mapped significant en echelon arrays of knolls and ridges on the NNW-trending Nosappu Fracture Zone between Hokkaido and Shatsky Rise, NW Pacific. This fracture zone has been known to be irregular, including a deep-sea channel, the Nakwe Channel, enigmatic for inside the wide oceanic plate. Considering the previously recognized magnetic lineament dislocation, the fracture zone has long (more than 150 km) left-lateral strike-slip component as a ridge-ridge transform fault zone between the Izanagi and Pacific plates during Early Cretaceous. Detail multi-narrowbeam mapping around 37 N latitude, 150 E longitude (covering 78 km x 137 km), indicated many small knolls and ridges that form en echelon arrangement. Some are boomerang, sock or E-letter in shape. The two dominant directions of ridges are recognized, one is parallel to the fracture zone and the other is in left-handed en echelon fashion. Besides these ridges, there are other types of ridges or conical knolls lower than 500 m in relief; one is a group of rather large knolls extending to NE, roughly perpendicular to the fracture zone direction, and the other is independent small knolls, summing up to five or six in number. Another expression of a depression zone was recognized with a moderate angle to the fracture zone in a crank fashion. This may correspond to the so-called _gNakwe Channel_h which has been wrongly mistaken. Such en echelon arrays are involved in a 50 km wide NNW-SSE zone, which is sharply demarcated by fault scarps. These characteristics in the fracture zone area and associated knolls suggest that this part of the Nosappu Fracture Zone might have developed in a fault interaction area which has a left-lateral component of leaky transform faulting close to the spreading ridge.

  17. Back pain in adults.

    Science.gov (United States)

    Becker, Jonathan A; Stumbo, Jessica R

    2013-06-01

    This article provides a summary of the many causes of back pain in adults. There is an overview of the history and physical examination with attention paid to red flags that alert the clinician to more worrisome causes of low back pain. An extensive differential diagnosis for back pain in adults is provided along with key historical and physical examination findings. The various therapeutic options are summarized with an emphasis on evidence-based findings. These reviewed treatments include medication, physical therapy, topical treatments, injections, and complementary and alternative medicine. The indications for surgery and specialty referral are also discussed.

  18. Pollution concentration estimates in ecologically important zones

    Energy Technology Data Exchange (ETDEWEB)

    Skiba, Y.N. [Mexico City Univ. (Mexico). Center for Atmospheric Sciences

    1995-12-31

    Method based on using the pollutant transport equation and the adjoint technique is described here for estimating the pollutant concentration level in ecologically important zones. The method directly relates the pollution level in such zones with the power of the pollution sources and the initial pollution field. Assuming that the wind or current velocities are known (from climatic data or dynamic model), the main and adjoint pollutant transport equations can be considered in a limited area to solve such theoretically and practically important problems as: (1) optimal location of new industries in a given region with the aim to minimize the pollution concentration in certain ecologically important zones, (2) optimization of emissions from operating industries, (3) detection of the plants violating sanitary regulations, (4) analysis of the emissions coming from the vehicle traffic (such emissions can be included in the model by means of the linear pollution sources located along the main roadways), (5) estimation of the oil pollution in various ecologically important oceanic (sea) zones in case of accident with the oil tanker, (6) evaluation of the sea water desalination level in estuary regions, and others. These equations considered in a spherical shell domain can also be applied to the problems of transporting the pollutants from a huge industrial complex, or from the zone of an ecological catastrophe similar to the Chernobyl one

  19. Mesopelagic zone ecology and biogeochemistry - a synthesis

    Science.gov (United States)

    Robinson, Carol; Steinberg, Deborah K.; Anderson, Thomas R.; Arístegui, Javier; Carlson, Craig A.; Frost, Jessica R.; Ghiglione, Jean-François; Hernández-León, Santiago; Jackson, George A.; Koppelmann, Rolf; Quéguiner, Bernard; Ragueneau, Olivier; Rassoulzadegan, Fereidoun; Robison, Bruce H.; Tamburini, Christian; Tanaka, Tsuneo; Wishner, Karen F.; Zhang, Jing

    2010-08-01

    The mesopelagic zone is the oceanic region through which carbon and other elements must pass in order to reach deeper waters or the sea floor. However, the food web interactions that occur in the mesopelagic zone are difficult to measure and so, despite their crucial importance to global elemental cycles, are not very well known. Recent developments in technology and new approaches have advanced the study of the variability in and controls upon the distribution and diversity of organisms in the mesopelagic zone, including the roles of respiration, recycling, and repackaging of particulate and dissolved organic material. However, there are remarkably few syntheses of the ecology and biogeochemistry of the microbes and metazoa that permanently reside or habitually visit this 'twilight zone'. Without this synthesis, it is difficult to assess the impact of ongoing changes in ocean hydrography and chemistry, due to increasing atmospheric carbon dioxide levels, on the biological carbon pump. This paper reviews what is known about the distribution of microbes and metazoa in the mesopelagic zone in relation to their activity and impact on global biogeochemical cycles. Thus, gaps in our knowledge are identified and suggestions made for priority research programmes that will improve our ability to predict the effects of climate change on carbon sequestration.

  20. Risk-based zoning for urbanizing floodplains.

    Science.gov (United States)

    Porse, Erik

    2014-01-01

    Urban floodplain development brings economic benefits and enhanced flood risks. Rapidly growing cities must often balance the economic benefits and increased risks of floodplain settlement. Planning can provide multiple flood mitigation and environmental benefits by combining traditional structural measures such as levees, increasingly popular landscape and design features (green infrastructure), and non-structural measures such as zoning. Flexibility in both structural and non-structural options, including zoning procedures, can reduce flood risks. This paper presents a linear programming formulation to assess cost-effective urban floodplain development decisions that consider benefits and costs of development along with expected flood damages. It uses a probabilistic approach to identify combinations of land-use allocations (residential and commercial development, flood channels, distributed runoff management) and zoning regulations (development zones in channel) to maximize benefits. The model is applied to a floodplain planning analysis for an urbanizing region in the Baja Sur peninsula of Mexico. The analysis demonstrates how (1) economic benefits drive floodplain development, (2) flexible zoning can improve economic returns, and (3) cities can use landscapes, enhanced by technology and design, to manage floods. The framework can incorporate additional green infrastructure benefits, and bridges typical disciplinary gaps for planning and engineering.

  1. GEODESIC RECONSTRUCTION, SADDLE ZONES & HIERARCHICAL SEGMENTATION

    Directory of Open Access Journals (Sweden)

    Serge Beucher

    2011-05-01

    Full Text Available The morphological reconstruction based on geodesic operators, is a powerful tool in mathematical morphology. The general definition of this reconstruction supposes the use of a marker function f which is not necessarily related to the function g to be built. However, this paper deals with operations where the marker function is defined from given characteristic regions of the initial function f, as it is the case, for instance, for the extrema (maxima or minima but also for the saddle zones. Firstly, we show that the intuitive definition of a saddle zone is not easy to handle, especially when digitised images are involved. However, some of these saddle zones (regional ones also called overflow zones can be defined, this definition providing a simple algorithm to extract them. The second part of the paper is devoted to the use of these overflow zones as markers in image reconstruction. This reconstruction provides a new function which exhibits a new hierarchy of extrema. This hierarchy is equivalent to the hierarchy produced by the so-called waterfall algorithm. We explain why the waterfall algorithm can be achieved by performing a watershed transform of the function reconstructed by its initial watershed lines. Finally, some examples of use of this hierarchical segmentation are described.

  2. 78 FR 5717 - Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

    Science.gov (United States)

    2013-01-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal Concord, CA AGENCY: Coast Guard, DHS. ACTION: Interim rule and... Suisun Bay near Military Ocean Terminal Concord, CA in support of military onload and offload...

  3. 75 FR 16370 - Regulated Navigation Areas, Safety Zones, Security Zones; Deepwater Ports in Boston Captain of...

    Science.gov (United States)

    2010-04-01

    ... standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling... do not individually or cumulatively have a significant effect on the human environment. A preliminary... zones for Neptune consist of circular zones, each with a 500-meter radius and centered on each...

  4. 76 FR 41073 - Security Zones; Sector Southeastern New England Captain of the Port Zone

    Science.gov (United States)

    2011-07-13

    ... cruise ship anchored or moored, and 200-yard radius security zone encompassing all navigable waters around any cruise ship underway that is being escorted by Coast Guard or law enforcement agencies.... These security zones will be activated and enforced only when a cruise ship is transiting, anchored,...

  5. 23 CFR 750.708 - Acceptance of state zoning.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Acceptance of state zoning. 750.708 Section 750.708... BEAUTIFICATION Outdoor Advertising Control § 750.708 Acceptance of state zoning. (a) 23 U.S.C. 131(d) provide...) further provides, “The States shall have full authority under their own zoning laws to zone areas...

  6. Zoning for Day Care (from Models for Day Care Licensing).

    Science.gov (United States)

    Day Care and Child Development Council of America, Inc., Washington, DC.

    Recommendations and regulations regarding the zoning of child development day care programs are discussed. Zoning in general is discussed, as is the treatment of child development day care in zoning ordinance, the background of program planning, modular housing, the impelmentation of zoning, and model provisions regarding characteristics of…

  7. 33 CFR 334.5 - Disestablishment of a danger zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Disestablishment of a danger zone..., DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.5 Disestablishment of a danger zone. (a) Upon receipt of a request from any agency for the disestablishment of a danger zone, the...

  8. 33 CFR 2.30 - Exclusive Economic Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Exclusive Economic Zone. 2.30... JURISDICTION Jurisdictional Terms § 2.30 Exclusive Economic Zone. (a) With respect to the United States... States exercises sovereignty, exclusive economic zone means the zone seaward of and adjacent to...

  9. 49 CFR 1105.9 - Coastal Zone Management Act requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Coastal Zone Management Act requirements. 1105.9... ENVIRONMENTAL LAWS § 1105.9 Coastal Zone Management Act requirements. (a) If the proposed action affects land or water uses within a State coastal zone designated pursuant to the Coastal Zone Management Act (16...

  10. Dynamics of Vadose Zone Transport: a Field and Modeling Study using the Vadose Zone Observatory

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, C R

    2001-01-01

    A stated need of the DOE EM program is a better understanding of basic vadose zone fluid flow and contaminant transport processes for the purpose of making improved estimates of contaminant release rates and fluxes across the vadose zone to the water table at DOE sites such as the tank farms at Hanford. We investigate details of the modes of contaminant transport with the aid of infiltration experiments designed to elucidate how vadose zone characteristics such as preferential pathways, heterogeneities, and relative permeabilities influence the transport of contamination in liquid, gas and colloidal phases to the water table. Beyond enhancing our basic understanding of vadose zone transport processes, this EMSP project is designed result in a vadose-zone-transport-characterization methodology that can be generalized to other DOE sites.

  11. The 'Goldilocks Zone': getting the measure of manual asymmetries.

    Directory of Open Access Journals (Sweden)

    Rachael K Raw

    Full Text Available Some studies have shown that manual asymmetries decrease in older age. These results have often been explained with reference to models of reduced hemispheric specialisation. An alternative explanation, however, is that hand differences are subtle, and capturing them requires tasks that yield optimal performance with both hands. Whereas the hemispheric specialisation account implies that reduced manual asymmetries should be reliably observed in older adults, the 'measurement difficulty' account suggests that manual asymmetries will be hard to detect unless a task has just the right level of difficulty--i.e. within the 'Goldilocks Zone', where it is not too easy or too hard, but just right. Experiment One tested this hypothesis and found that manual asymmetries were only detected when participants performed in this zone; specifically, performance on a tracing task was only superior in the preferred hand when task constraints were high (i.e. fast speed tracing. Experiment Two used three different tasks to examine age differences in manual asymmetries; one task produced no asymmetries, whilst two tasks revealed asymmetries in both younger and older groups (with poorer overall performance in the old group across all tasks. Experiment Three revealed task-dependent asymmetries in both age groups, but highlighted further detection difficulties linked with the metric of performance and compensatory strategies used by participants. Results are discussed with reference to structural learning theory, whereby we suggest that the processes of inter-manual transfer lead to relatively small performance differences between the hands (despite a strong phenomenological sense of performance disparities.

  12. Zoned electrical heater arranged in spaced relationship from particulate filter

    Science.gov (United States)

    Gonze, Eugene V [Pinckney, MI

    2011-11-15

    A system comprises a particulate matter (PM) filter that comprises an upstream end for receiving exhaust gas and a downstream end. A zoned heater is arranged spaced from the upstream end and comprises N zones, where N is an integer greater than one, wherein each of the N zones comprises M sub-zones, where M is an integer greater than one. A control module selectively activates at least a selected one of the N zones to initiate regeneration in downstream portions of the PM filter from the one of the N zones and deactivates non-selected ones of the N zones.

  13. Urban planning as a trading zone

    CERN Document Server

    Mäntysalo, Raine

    2013-01-01

    'Trading zone' is a concept introduced by Peter Galison in his social scientific research on how scientists representing different sub-cultures and paradigms have been able to coordinate their interaction locally. In this book, Italian and Finnish planning researchers extend the use of the concept to different contexts of urban planning and management, where there is a need for new ideas and tools in managing the interaction of different stakeholders. The trading zone concept is approached as a tool in organizing local platforms and support systems for planning participation, knowledge production, decision making and local conflict management. In relation to the former theses of communicative planning theory that stress the ideals of consensus, mutual understanding and universal reason, the 'trading zone approach', outlined in this book, offers a different perspective. It focuses on the potentiality to coordinate locally the interaction of different stakeholders without requiring the deeper sharing of underst...

  14. Subduction zones seen by GOCE gravity gradients

    DEFF Research Database (Denmark)

    Švarc, Mario; Herceg, Matija; Cammarano, Fabio

    In this study, the GOCE (Gravity field and steady state Ocean Circulation Explorer) gradiometry data were used to study geologic structures and mass variations within the lithosphere in areas of known subduction zones. The advantage of gravity gradiometry over other gravity methods...... is that gradients are extremely sensitive to localized density contrasts within regional geological settings, which makes it ideally suited for detecting subduction zones. Second order gravity gradients of disturbing potential were extracted from global geopotential model, the fifth release GOCE model ‘EGM_TIM_RL05......’. In order to remove the signal which mainly corresponds to the gravity signal of the lower mantle, long wavelength part of the gravity signal was removed up to degree and order 60. Because the areas with notable topography differences coincide with subduction zones, topography correction was also performed...

  15. A systems approach framework for coastal zones

    DEFF Research Database (Denmark)

    Hopkins, Tom Sawyer; Bailly, Denis; Støttrup, Josianne

    2011-01-01

    This Special Feature Volume examines the potential value of the Systems Approach Framework (SAF) as a methodological framework for the transition to sustainable development in coastal zones. This article provides insight on the Systems Approach, the theory behind it, and how its practical...... application to coastal zone systems (CZSs) was developed. The SAF is about information for management through a focus on how to generate a higher, dynamic level of information about complex CZSs and how to render this information more useful to end users through a participatory suite of communication methods...... of this Volume synthesizes these results in the context of the SAF as a higher level instrument for integrated coastal zone management...

  16. Magnetic Fields in the Solar Convection Zone

    Directory of Open Access Journals (Sweden)

    Yuhong Fan

    2009-12-01

    Full Text Available Active regions on the solar surface are generally thought to originate from a strong toroidal magnetic field generated by a deep seated solar dynamo mechanism operating at the base of the solar convection zone. Thus the magnetic fields need to traverse the entire convection zone before they reach the photosphere to form the observed solar active regions. Understanding this process of active region flux emergence is therefore a crucial component for the study of the solar cycle dynamo. This article reviews studies with regard to the formation and rise of active region scale magnetic flux tubes in the solar convection zone and their emergence into the solar atmosphere as active regions.

  17. Seismomagnetic response of a fault zone

    Science.gov (United States)

    Adushkin, V. V.; Loktev, D. N.; Spivak, A. A.

    2017-01-01

    Based on the results of instrumental observations of geomagnetic variations caused by the propagation of seismic waves through a fault zone, the dependences between the amplitudes of the induced seismomagnetic effect and seismic signal as a function of distance r to the midline of the fault are obtained. For the first time, it is shown that the amplitude of the seismomagnetic effect is maximal in the fault damage zone. The phenomenological model describing the generation of magnetic signals by seismic waves propagating through the crushed rock in the tectonic fault zone is suggested. It is assumed that geomagnetic variations are generated by the changes in the electrical conductivity of the fragmented rocks as a result of the deformation of the rock pieces contacts. The amplitudes of the geomagnetic variations calculated from the model agree with the instrumental observations.

  18. Multi-zone cooling/warming garment

    Science.gov (United States)

    Koscheyev, Victor S. (Inventor); Leon, Gloria R. (Inventor); Dancisak, Michael J. (Inventor)

    2006-01-01

    A thermodynamically efficient garment for cooling and/or heating a human body. The thermodynamic efficiency is provided in part by targeting the heat exchange capabilities of the garment to specific areas and/or structures of the human body. The heat exchange garment includes heat exchange zones and one or more non-heat exchange zones, where the heat exchange zones are configured to correspond to one or more high density tissue areas of the human body when the garment is worn. A system including the garment can be used to exchange heat with the adjacent HD tissue areas under the control of a feedback control system. Sensed physiological parameters received by the feedback control system can be used to adjust the characteristics of heat exchange fluid moving within the heat exchange garment.

  19. Compositional zoning of the bishop tuff

    Science.gov (United States)

    Hildreth, W.; Wilson, C.J.N.

    2007-01-01

    Compositional data for >400 pumice clasts, organized according to eruptive sequence, crystal content, and texture, provide new perspectives on eruption and pre-eruptive evolution of the >4600 km3 of zoned rhyolitic magma ejected as the BishopTuff during formation of Long Valley caldera. Proportions and compositions of different pumice types are given for each ignimbrite package and for the intercalated plinian pumice-fall layers that erupted synchronously. Although withdrawal of the zoned magma was less systematic than previously realized, the overall sequence displays trends toward greater proportions of less evolved pumice, more crystals (0-5 24 wt %), and higher FeTi-oxide temperatures (714-818??C). No significant hiatus took place during the 6 day eruption of the BishopTuff, nearly all of which issued from an integrated, zoned, unitary reservoir. Shortly before eruption, however, the zoned melt-dominant portion of the chamber was invaded by batches of disparate lower-silica rhyolite magma, poorer in crystals than most of the resident magma but slightly hotter and richer in Ba, Sr, andTi. Interaction with resident magma at the deepest levels tapped promoted growth ofTi-rich rims on quartz, Ba-rich rims on sanidine, and entrapment of near-rim melt inclusions relatively enriched in Ba and CO2.Varied amounts of mingling, even in higher parts of the chamber, led to the dark gray and swirly crystal-poor pumices sparsely present in all ashflow packages. As shown by FeTi-oxide geothermometry, the zoned rhyolitic chamber was hottest where crystal-richest, rendering any model of solidification fronts at the walls or roof unlikely.The main compositional gradient (75-195 ppm Rb; 0.8-2.2 ppm Ta; 71-154 ppm Zr; 0.40-1.73% FeO*) existed in the melt, prior to crystallization of the phenocryst suite observed, which included zircon as much as 100 kyr older than the eruption.The compositions of crystals, though themselves largely unzoned, generally reflect magma temperature and

  20. Dance for Older Adults.

    Science.gov (United States)

    Pruett, Diane Milhan, Ed.; And Others

    1983-01-01

    Dance programs for older adults that encourage exercise and socializing are described in six articles. Program guidelines of the American Alliance Committee on Aging are explained, and other articles emphasize a movement education approach that may involve intergenerational contact. A dance program held in a worship setting is also discussed. (PP)

  1. Inguinal Herniography in adults

    Energy Technology Data Exchange (ETDEWEB)

    Kim, B. T.; Park, K. J. [57th Evacuation Hospital, Korea Army, Seoul (Korea, Republic of); Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1980-06-15

    Inguinal hernia in children is easily diagnosed in most cases: however, it is sometimes different or impossible to detect by physical examination. The some is true of a contralateral asymptomatic hernia. White have reported that herniography is easy to perform and has a high degree of accuracy and minimal morbidity. The diagnostic accuracy of herniography in detection of patent process vaginalis is 95-98% by white. Rowe found 40% of children over age of of 2 years and adults with a unilateral congenital hernia had an open process vaginalis in contralateral normal site and concluded that 20% of patients with a unilateral hernia will develop a contralateral hernia sometimes during life. It is necessary to check the condition of the normal site before surgery in unilateral hernia by herniogram. But in adults, the hernigraphy was not performed due to some reason. We found that the herniography in adults is also easy ro perform and high degree of accuracy. The results are: 1. Total number of studies are 25 patient of unilateral inguinal hernia. 2. We found 32% of adults male with unilateral hernia had an open process viginalis in contralateral normal site. 3. Slight more abdominal disconfort than children is noted during injection of Hypaque. 4. Prominent lateral recess of Douglaspouch and poor coating of contrast media to peritoneum are different radiologic finding from children.

  2. Facilitation of Adult Development

    Science.gov (United States)

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  3. Police and Adult Education.

    Science.gov (United States)

    Sims, Vic

    The literature on adult education for police is reviewed and criticized. Among the publications that have been influential in debating the need for police education are Charles B. Saunder's "The Challenge of Crime in a Free Society" (1976), which endorses the Presidential Commission on Law Enforcement's recommendations regarding the vital…

  4. Adult onset Leigh syndrome

    Directory of Open Access Journals (Sweden)

    Pandit Lekha

    2007-01-01

    Full Text Available Leigh syndrome is a rare progressive mitochondrial disorder of oxidative metabolism. Though it has been reported in infancy and childhood, it is rarely described in adults. The authors describe a patient who had clinical and magnetic resonance imaging features diagnostic of Leigh syndrome, with supportive biochemical and muscle histochemistry evidence.

  5. Adult issues in phenylketonuria.

    NARCIS (Netherlands)

    Hoeks, M.P.; Heijer, M. den; Janssen, M.C.H.

    2009-01-01

    Phenylketonuria (PKU) is a classical example of an inherited metabolic disease, in which mental retardation can be prevented successfully by using a diet. However, in adult PKU new problems occur, such as vitamin deficiencies, osteoporosis and the maternal PKU syndrome. The aim of this review articl

  6. Adult intergenerational relationships

    NARCIS (Netherlands)

    Kalmijn, M.; Treas, J.; Scott, J.; Richards, M.

    2014-01-01

    This chapter gives an overview of research on the relationships between parents and their adult, grown-up children. Interest in intergenerational ties has increased again as a result of the aging of Western societies. The chapter discusses the following topics in the literature: (i) the degree to wh

  7. Depression - older adults

    Science.gov (United States)

    ... slowly than in younger adults. To better manage depression at home: Exercise regularly, if the provider says it is OK. Surround yourself with caring, positive people and do fun activities. ... signs of depression, and know how to react if these occur. ...

  8. Smoking and Older Adults

    Centers for Disease Control (CDC) Podcasts

    2008-10-27

    This podcast discusses the importance of older adults quitting smoking and other tobacco products. It is primarily targeted to public health and aging services professionals.  Created: 10/27/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/20/2008.

  9. Migration and Adult Education

    Science.gov (United States)

    Gois, William

    2007-01-01

    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  10. Tracking adult stem cells

    NARCIS (Netherlands)

    Snippert, H.J.G.; Clevers, H.

    2011-01-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue--known as their niche--and thus, stem-cell studies should preferably be performed in a physiological context,

  11. Adult Education in Brazil.

    Science.gov (United States)

    Ministerio da Educacao e Cultura, Rio de Janeiro (Brazil).

    The status and goals of adult education programs in Brazil are discussed in this report. Supplemental systems such as the Brazilian Literacy Movement (Mobral) and their results are described and evaluated. Charts detailing the evolution of literacy are shown and priorities in education are suggested. The progress of other educational entities is…

  12. Adult educators' core competences

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne

    2016-01-01

    environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or “core...

  13. More Adults Are Walking

    Centers for Disease Control (CDC) Podcasts

    2012-07-31

    This podcast is based on the August 2012 CDC Vital Signs report. While more adults are walking, only half get the recommended amount of physical activity. Listen to learn how communities, employers, and individuals may help increase walking.  Created: 7/31/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/7/2012.

  14. Adult Education in Beijing

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    The Chinese University of Science and Technology, Management and Administration, run by the local people, has achieved great success in adult edu cation. Jiang Shuyun (3rd L), head of the university, won the title of advanced industrialist from the State Science and Technology Commission.

  15. Unsaturated Zone Flow Model Expert Elicitation Project

    Energy Technology Data Exchange (ETDEWEB)

    Coppersmith, K. J.

    1997-05-30

    This report presents results of the Unsaturated Zone Flow Model Expert Elicitation (UZFMEE) project at Yucca Mountain, Nevada. This project was sponsored by the US Department of Energy (DOE) and managed by Geomatrix Consultants, Inc. (Geomatrix), for TRW Environmental Safety Systems, Inc. The objective of this project was to identify and assess the uncertainties associated with certain key components of the unsaturated zone flow system at Yucca Mountain. This assessment reviewed the data inputs, modeling approaches, and results of the unsaturated zone flow model (termed the ''UZ site-scale model'') being developed by Lawrence Berkeley National Laboratory (LBNL) and the US Geological Survey (USGS). In addition to data input and modeling issues, the assessment focused on percolation flux (volumetric flow rate per unit cross-sectional area) at the potential repository horizon. An understanding of unsaturated zone processes is critical to evaluating the performance of the potential high-level nuclear waste repository at Yucca Mountain. A major goal of the project was to capture the uncertainties involved in assessing the unsaturated flow processes, including uncertainty in both the models used to represent physical controls on unsaturated zone flow and the parameter values used in the models. To ensure that the analysis included a wide range of perspectives, multiple individual judgments were elicited from members of an expert panel. The panel members, who were experts from within and outside the Yucca Mountain project, represented a range of experience and expertise. A deliberate process was followed in facilitating interactions among the experts, in training them to express their uncertainties, and in eliciting their interpretations. The resulting assessments and probability distributions, therefore, provide a reasonable aggregate representation of the knowledge and uncertainties about key issues regarding the unsaturated zone at the Yucca

  16. Pathogenesis of splenic marginal zone lymphoma

    Directory of Open Access Journals (Sweden)

    Ming-Qing Du

    2015-11-01

    Full Text Available Splenic marginal zone lymphoma (SMZL is a distinct low grade B-cell lymphoma with an immunophenotype similar to that of splenic marginal zone B-cells. Like the normal splenic marginal zone B-cells, SMZLs also show variable features in somatic mutations of their rearranged immunoglobulin genes, with ∼90% of cases harbouring somatic mutations but at remarkably variable degrees, suggesting that SMZL may have multiple cell of origins, deriving from the heterogeneous B-cells of the splenic marginal zone. Notably, ∼30% of SMZLs show biased usage of IGHV1-2*04, with the expressed BCR being potentially polyreactive to autoantigens. Recent exome and targeted sequencing studies have identified a wide spectrum of somatic mutations in SMZL with the recurrent mutations targeting multiple signalling pathways that govern the development of splenic marginal zone B-cells. These recurrent mutations occur in KLF2 (20–42%, NOTCH2 (6.5–25%, NF-κB (CARD11 ∼7%, IKBKB ∼7%, TNFAIP3 7–13%, TRAF3 5%, BIRC3 6.3% and TLR (MYD88 5–13% signalling pathways. Interestingly, the majority of SMZL with KLF2 mutation have both 7q32 deletion and IGHV1-2 rearrangement, and these cases also have additional mutations in NOTCH2, or TNFAIP3, or TRAF3. There is a potential oncogenic cooperation among concurrent genetic changes, for example between the IGHV1-2 expressing BCR and KLF2 mutation in activation of the canonical NF-κB pathway, and between KLF2 and TRAF3 mutations in activation of the non-canonical NF-κB pathway. These novel genetic findings have provided considerable insights into the pathogenesis of SMZL and will stimulate the research in both normal and malignant marginal zone B-cells.

  17. SAR observations of coastal zone conditions

    Science.gov (United States)

    Meadows, G. A.; Kasischke, E. S.; Shuchman, R. A.

    1980-01-01

    Applications of Synthetic Aperture Radar (SAR) technology to the observation of coastal zones phenomena are detailed. The conditions observed include gravity wave detection, surf zone location, surface currents, and long-period 'surf beats'. Algorithms have been developed and successfully tested that determine significant wave and current parameters from the sea surface backscatter of microwave energy. Doppler information from the SAR optical correlator allows a rough estimation of near shore surface flow velocities that has been found in agreement with both theory and in situ observations as well. Seasat SAR data of the Scotland and North Carolina coasts are considered, as well as the results of bathymetric updating of coastal area charts.

  18. Building fire zone model with symbolic mathematics

    Institute of Scientific and Technical Information of China (English)

    武红梅; 郜冶; 周允基

    2009-01-01

    To apply the fire modelling for the fire engineer with symbolic mathematics,the key equations of a zone model were demonstrated. There were thirteen variables with nine constraints,so only four ordinary differential equations (ODEs) were required to solve. A typical fire modelling with two-room structure was studied. Accordingly,the source terms included in the ODEs were simplified and modelled,and the fourth Runge-Kutta method was used to solve the ordinary differential equations (ODEs) with symbolic mathematics. Then a zone model could be used with symbolic mathematics. It is proposed that symbolic mathematics is possible for use by fire engineer.

  19. Recent Study of the Changjiang Fault Zone

    Institute of Scientific and Technical Information of China (English)

    Hou Kangming; Zong Kaihong; Guo Jiangning; Xiong Zhen; Li Limei; Zhou Caixia; Jiang Bo

    2009-01-01

    The Changjiang fault zone, also known as the Mufushan-Jiaoshan fault, is a famous fault located at the southern bank of the Changjiang River, near the Nanjing downtown area. Based on multidisciplinary data from shallow artificial seismic explorations in the target detecting area (Nanjing city and the nearby areas), trenching and drilling explorations, classification of Quaternary strata and chronology dating data, this paper provides the most up-to-date results regarding activities of the Changjiang fault zone, including the most recent active time, activity nature, related active parameters, and their relation to seismic activity.

  20. La zone nouvelle de Pudong (Shangai

    Directory of Open Access Journals (Sweden)

    Gabriel Weissberg

    2000-09-01

    Full Text Available Depuis 1990 et au prix de lourds investissements en infrastructures, le gouvernement et les autorités locales espèrent faire de la Zone Nouvelle de Pudong un élément clé de l’expansion de Shanghai. Neuf zones d’activités accueillent habitat, services et industries. Le développement de la ZNP reste cependant marqué par certaines faiblesses qui posent la question de son rôle dans le renouveau attendu de Shanghai.

  1. 33 CFR 3.40-35 - Sector Corpus Christi Marine Inspection Zone and Captain of the Port Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sector Corpus Christi Marine... ZONES, AND CAPTAIN OF THE PORT ZONES Eighth Coast Guard District § 3.40-35 Sector Corpus Christi Marine Inspection Zone and Captain of the Port Zone. Sector Corpus Christi's office is located in Corpus Christi,...

  2. 32 CFR 256.9 - Real estate interests to be considered for clear zones and accident potential zone.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Real estate interests to be considered for clear zones and accident potential zone. 256.9 Section 256.9 National Defense Department of Defense (Continued....9 Real estate interests to be considered for clear zones and accident potential zone. (a) The...

  3. 33 CFR 165.169 - Safety and Security Zones: New York Marine Inspection Zone and Captain of the Port Zone.

    Science.gov (United States)

    2010-07-01

    ... Point, NY; and Coast Guard Aids to Navigation Team New York, Bayonne, NJ. (3) Part 105 Facilities—(i) Definition. For the purposes of this section, Part 105 Facility means any facility subject to the regulations... that security zone is not being enforced. (13) Liquefied Hazardous Gas (LHG) Vessels—(i)...

  4. Teaching Nontraditional Adult Students: Adult Learning Theories in Practice

    Science.gov (United States)

    Chen, Joseph C.

    2014-01-01

    As the USA experiences rapid growth of nontraditional adult students in higher education, educators and institutions will increasingly need to look beyond the traditional youth-centric educational models to better address adult learning needs. To date, no research has been conducted examining the learning experiences of adult students enrolled in…

  5. Traffic Analysis Zones - TRAFFIC_ZONES_TIGER00_IN: Indiana Traffic Analysis Zones (U.S. Census Bureau, 1:100,000, Polygon Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — TRAFFIC_ZONES_TIGER00_IN contains traffic analysis zones in Indiana identified by the US Bureau of the Census. Vigo, Madison, and Monroe counties were not available...

  6. Bottom-up effects of a no-take zone on endangered penguin demographics.

    Science.gov (United States)

    Sherley, Richard B; Winker, Henning; Altwegg, Res; van der Lingen, Carl D; Votier, Stephen C; Crawford, Robert J M

    2015-07-01

    Marine no-take zones can have positive impacts for target species and are increasingly important management tools. However, whether they indirectly benefit higher order predators remains unclear. The endangered African penguin (Spheniscus demersus) depends on commercially exploited forage fish. We examined how chick survival responded to an experimental 3-year fishery closure around Robben Island, South Africa, controlling for variation in prey biomass and fishery catches. Chick survival increased by 18% when the closure was initiated, which alone led to a predicted 27% higher population compared with continued fishing. However, the modelled population continued to decline, probably because of high adult mortality linked to poor prey availability over larger spatial scales. Our results illustrate that small no-take zones can have bottom-up benefits for highly mobile marine predators, but are only one component of holistic, ecosystem-based management regimes.

  7. Stages of Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  8. Congenital Heart Disease in Adults

    Science.gov (United States)

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  9. Alcohol Use and Older Adults

    Science.gov (United States)

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  10. Spleen removal - open - adults - discharge

    Science.gov (United States)

    Splenectomy - adult - discharge; Spleen removal - adult - discharge ... You had surgery to remove your spleen. This operation is called splenectomy . The surgeon made a cut (incision) in the middle of your belly or on the left side ...

  11. Adult Education for Social Mobilization.

    Science.gov (United States)

    Echeverria, Luis

    1981-01-01

    Suggests some ideas that could stimulate and be incentives for defining programs of adult education in the future. These involve changing priorities, developing a framework which allows adult education programs to be established, and managing decision-making processes. (CT)

  12. Stroke: Unique to Older Adults

    Science.gov (United States)

    ... Failure High Blood Pressure Managing Multiple Health Problems Osteoporosis Urinary Incontinence Join our e-newsletter! Aging & Health A to Z Stroke Unique to Older Adults This section provides information to help older adults ...

  13. Older Adults (and Oral Health)

    Science.gov (United States)

    ... Health Information Sorted by ... > OlderAdults Older Adults and Oral Health Main Content ​ Is dry mouth a natural part ... from fiction by reading this web page about oral health and growing older. Having the right information can ...

  14. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  15. Renal Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  16. HIV Infection and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals HIV Infection and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... percentage is less than 15%. Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  17. Dengue fever and dengue haemorrhagic fever in adolescents and adults.

    Science.gov (United States)

    Tantawichien, Terapong

    2012-05-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients.

  18. Telocytes in meninges and choroid plexus.

    Science.gov (United States)

    Popescu, B O; Gherghiceanu, M; Kostin, S; Ceafalan, L; Popescu, L M

    2012-05-16

    Telocytes (TCs) are a recently identified type of interstitial cells present in a wide variety of organs in humans and mammals (www.telocytes.com). They are characterized by a small cell body, but extremely long cell processes - telopodes (Tp), and a specific phenotype. TCs establish close contacts with blood capillaries, nerve fibers and stem cells. We report here identification of TCs by electron microscopy and immunofluorescence in rat meninges and choroid plexus/subventricular zone, in the vicinity of putative stem cells. The presence of TCs in brain areas involved in adult neurogenesis might indicate that they have a role in modulation of neural stem cell fate.

  19. Personal Factors as Determinants of Utilization of Development Information in Rural Communities of South-South Geo-Political Zone, Nigeria

    Science.gov (United States)

    Edet, Itari Paul; Bullem, Anthony Godwin; Okeme, Isaac

    2015-01-01

    This study investigated the extent to which personal factors relate to the utilization of development information in the rural communities of South-South Geo-political Zone, Nigeria. The study adopted the descriptive survey design. The population comprised all adult male and female rural dwellers from the three out of the six states in the Zone…

  20. Ectoparasites of sheep in three agro-ecological zones in central Oromia, Ethiopia

    Directory of Open Access Journals (Sweden)

    Bersissa Kumsa

    2012-10-01

    Full Text Available A cross-sectional study was conducted to determine the prevalence and risk factors for ectoparasites infestation in sheep in three agro-ecological zones in central Oromia, Ethiopia, from October 2009 to April 2010. The study revealed that 637 (48.1% of the 1325 sheep examined were infested with one or more ectoparasites. The ectoparasites identified were Bovicola ovis (27.2%, Melophagus ovinus (16.4%, Ctenocephalides sp. (2.3%, Linognathus africanus (1.2%, Linognathus ovillus (0.3%, Sarcoptes sp. (1.2%, Amblyomma variegatum (4.4%, Rhipicephalus evertsi evertsi (1.9%, Rhipicephalus pravus (1.9%, Rhipicephalus (Boophilus decoloratus (1.1%, Rhipicephalus sanguineus (0.9%, Rhipicephalus praetextatus (1.1% and Hyalomma truncatum (1.6%. Statistically significant difference was observed in prevalence of B. ovis amongst study agroecological zones: highland 36.6%, midland 20.9% and lowland 14.0%. Significantly higher prevalence was recorded in highland agroecological zone. A significantly (OR = 0.041, p 0.05 was never recorded in the prevalence of all the identified species of ectoparasites between male and female sheep hosts. However, a significantly (p = 0.006 higher prevalence of B. ovis was recorded between young and adult sheep. The risk of B. ovis infestation was 1.45 times higher in young than the adult sheep. Furthermore, a significantly (p < 0.001 higher prevalence of M. ovinus, B. ovis and Sarcoptes sp. was found between sheep with poor and a good body condition. The ever increasing threat of ectoparasites on overall sheep productivity and tanning industry in Ethiopia warrants urgent control intervention. Further studies on the role of ectoparasites in transmission of diseases to sheep, zoonotic importance, comparative prevalence and load, and the importance of sheep as alternative hosts in different agroecological zones, breeds and management systems in Ethiopia are recommended so as to design applicable control programme in the country.