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Subgranular Zone (subgranular + zone)
Selected AbstractsEffect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor poolDEVELOPMENTAL DYNAMICS, Issue 7 2008Nina Solberg Abstract Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages. Developmental Dynamics 237:1799,1811, 2008. © 2008 Wiley-Liss, Inc. [source] Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2010Anna Poon Abstract Neuron production takes place continuously in the rostral migratory stream (RMS) of the adult mammalian brain. The molecular mechanisms that regulate progenitor cell division and differentiation in the RMS remain largely unknown. Here, we surveyed the mouse genome in an unbiased manner to identify candidate gene loci that regulate proliferation in the adult RMS. We quantified neurogenesis in adult C57BL/6J and A/J mice, and 27 recombinant inbred lines derived from those parental strains. We showed that the A/J RMS had greater numbers of bromodeoxyuridine-labeled cells than that of C57BL/6J mice with similar cell cycle parameters, indicating that the differences in the number of bromodeoxyuridine-positive cells reflected the number of proliferating cells between the strains. AXB and BXA recombinant inbred strains demonstrated even greater variation in the numbers of proliferating cells. Genome-wide mapping of this trait revealed that chromosome 11 harbors a significant quantitative trait locus at 116.75 ± 0.75 Mb that affects cell proliferation in the adult RMS. The genomic regions that influence RMS proliferation did not overlap with genomic regions regulating proliferation in the adult subgranular zone of the hippocampal dentate gyrus. On the contrary, a different, suggestive locus that modulates cell proliferation in the subgranular zone was mapped to chromosome 3 at 102 ± 7 Mb. A subset of genes in the chromosome 11 quantitative trait locus region is associated with neurogenesis and cell proliferation. Our findings provide new insights into the genetic control of neural proliferation and an excellent starting point to identify genes critical to this process. [source] Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009Anja Haslinger Abstract In the mammalian brain, neural stem and progenitor cells in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus generate new neurons throughout adulthood. The generation of new functional neurons is a complex process that is tightly controlled by extrinsic signals and that is characterized by stage-specific gene expression programs and cell biological processes. The transcription factors regulating such stage-specific developmental steps in adult neurogenesis are largely unknown. Here we report that Sox11, a member of the group C Sox transcription factor family, is prominently expressed in the neurogenic areas of the adult brain. Further analysis revealed that Sox11 expression is strictly confined to doublecortin-expressing neuronally committed precursors and immature neurons but that Sox11 is not expressed in non-committed Sox2-expressing precursor cells and mature neurons of the adult neurogenic lineage. Finally, overexpression of Sox11 promotes the generation of doublecortin-positive immature neurons from adult neural stem cells in vitro. These data indicate that Sox11 is involved in the transcriptional regulation of specific gene expression programs in adult neurogenesis at the stage of the immature neuron. [source] Blockade of caspase-1 increases neurogenesis in the aged hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2007Carmelina Gemma Abstract Adult hippocampal neurogenesis dramatically decreases with increasing age, and it has been proposed that this decline contributes to age-related memory deficits. Central inflammation contributes significantly to the decrease in neurogenesis associated with ageing. Interleukin-1, is a proinflammatory cytokine initially synthesized as an inactive precursor that is cleaved by caspase-1 to generate the biologically active mature form. Whether IL-1, affects neurogenesis in the aged hippocampus is unknown. Here we analysed cells positive for 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg) in animals in which cleavage of IL-1, was inhibited by the caspase-1 inhibitor Ac-YVAD-CMK (10 pmol). Aged (22 months) and young (4 months) rats received Ac-YVAD-CMK for 28 days intracerebroventricularly through a brain infusion cannula connected to an osmotic minipump. Starting on day 14, animals received a daily injection of BrdU for five consecutive days. Unbiased stereology analyses performed 10 days after the last injection of BrdU revealed that the total number of newborn cells generated over a 5-day period was higher in young rats than in aged rats. In addition, there was a 53% increase in the number of BrdU-labelled cells of the aged Ac-YVAD-CMK-treated rats compared to aged controls. Immunofluorescence studies were performed to identify the cellular phenotype of BrdU-labelled cells. The increase in BrdU-positive cells was not due to a change in the proportion of cells expressing neuronal or glial phenotypes in the subgranular zone. These findings demonstrate that the intracerebroventricular administration of Ac-YVAD-CMK reversed the decrease in hippocampal neurogenesis associated with ageing. [source] N -methyl- d -aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following strokeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Andreas Arvidsson Abstract Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5-bromo-2,-deoxyuridine-5,-monophosphate (BrdU; injected during 4,6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N -methyl- d -aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis. [source] Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulbGENES TO CELLS, Issue 10 2006Naoko Kaneko Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress-induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions. [source] Cellular localization of epidermal-type and brain-type fatty acid-binding proteins in adult hippocampus and their response to cerebral ischemiaHIPPOCAMPUS, Issue 7 2010Dexuan Ma Abstract This study aimed at an analysis of expression of epidermal-type and brain-type fatty acid-binding proteins (E-FABP and B-FABP, also called FABP5 and FABP7, respectively) in adult hippocampus and their potential value as neuroprotective factors after ischemic brain damage in monkey model. The immunostaining and Western blotting results show that FABP5 was mainly expressed in neurons, whereas FABP7 was primarily expressed in astrocytes and progenitors of the subgranular zone (SGZ). Interestingly, FABP5 expression in neurons increased in cornu Ammonis 1 (CA1) and remains stable within dentate gyrus (DG) after ischemia; FABP7 expression increased within both CA1 and SGZ. This indicates a potential role for FABP5 and FABP7 in intracellular fatty acid transport within different neural cells. The change in FABP5,7 expression within CA1 and DG of the adult postischemic hippocampus was compatible with previous findings of downregulation in CA1 neurons and upregulation in SGZ progenitor cells after ischemia. Altogether, the present data suggest that polyunsaturated fatty acids, such as docosahexaenoic acid, may act via FABP5 or 7 to regulate adult postischemic hippocampal neuronal antiapoptosis or neurogenesis in primates. © 2009 Wiley-Liss, Inc. [source] Differential Effects of Stress on Adult Hippocampal Cell Proliferation in Low and High Aggressive MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2007A. H. Veenema Male wild house mice selected for a long (LAL) or a short (SAL) latency to attack a male intruder generally show opposing behavioural coping responses to environmental challenges. LAL mice, unlike SAL mice, adapt to novel challenges with a highly reactive hypothalamic-pituitary-adrenal axis and show an enhanced expression of markers for hippocampal plasticity. The present study aimed to test the hypothesis that these features of the more reactive LAL mice are reflected in parameters of hippocampal cell proliferation. The data show that basal cell proliferation in the subgranular zone (SGZ) of the dentate gyrus, assessed by the endogenous proliferation marker Ki-67, is lower in LAL than in SAL mice. Furthermore, application of bromodeoxyuridine (BrdU) over 3 days showed an almost two-fold lower cell proliferation rate in the SGZ in LAL versus SAL mice. Exposure to forced swimming resulted, 24 h later, in a significant reduction in BrdU + cell numbers in LAL mice, whereas cell proliferation was unaffected by this stressor in SAL mice. Plasma corticosterone and dentate gyrus glucocorticoid receptor levels were higher in LAL than in SAL mice. However, no differences between the SAL and LAL lines were found for hippocampal NMDA receptor binding. In conclusion, the data suggest a relationship between coping responses and hippocampal cell proliferation, in which corticosterone may be one of the determinants of line differences in cell proliferation responses to environmental challenges. [source] Inflammation: A new candidate in modulating adult neurogenesisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2008Sulagna Das Abstract Any pathological perturbation to the brain provokes a cascade of molecular and cellular events, which manifests in the form of microglial activation and release of various proinflammatory molecules. This eventually culminates in a profound neuroinflammatory reaction that characterizes the brain's response to stress, injury, or infection. The inflammatory cascade is an attempt by the system to eliminate the challenge imposed on the brain, clear the system of the dead and damaged neurons, and rescue the normal functioning of this vital organ. However, during the process of microglial activation, the proinflammatory mediators released exert certain detrimental effects, and neural stem cells and progenitor cells are likely to be affected. Here we review how the proliferation, maturation, and migration of the neural stem cells are modulated under such an inflammatory condition. The fate of the noncommitted neural stem cells and its differentiation potency are often under strict regulation, and these proinflammatory mediators seem to disrupt this critical balance and finely tune the neurogenesis pattern in the two niches of neurogenesis, the subventricular zone and the subgranular zone of the hippocampus. Moreover, the migration ability of these stem cells, which is important for localization to the proper site, is also affected in a major way by the chemokines released following inflammation. © 2007 Wiley-Liss, Inc. [source] Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemiaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2002Yoshiki Yagita Abstract Both nestin and the neural RNA-binding protein Musashi1 (Msi1) are expressed in neural stem cells in the subventricular zone. Neurogenesis in the hippocampus has received much attention, so we evaluated the expression of Msi1 and nestin in the adult rat hippocampus after transient forebrain ischemia. Both Msi1 and nestin were induced in the reactive astrocytes after ischemia, especially in the CA1 region, until 35 days after ischemia. Induction of both molecules suggested that reactive astrocytes might have immature characteristics. In the subgranular zone (SGZ) of the hippocampal dentate gyrus, Msi1-positive cells formed clusters after ischemia. These cells were labeled by bromodeoxyuridine (BrdU) but did not express glial fibrillary acidic protein. In contrast, very few nestin-positive cells were labeled by BrdU. Our results suggest that neuronal progenitor cells in the SGZ expressed Msi1 but not nestin. © 2002 Wiley-Liss, Inc. [source] Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2,-deoxyuridine-positive cells after inescapable shock in ratsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2008Akihito Kikuchi md Aim:, Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2,-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Methods:, Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. Results:, In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. Conclusion:, The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors. [source] Identification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brainTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 16 2010Yun-Yu Tseng Abstract Previous studies showed that Tctex-1 immunoreactivity is selectively enriched in the germinal zones of adult brain. In this report we identify a regulatory region of the Tctex-1 gene that is capable of directing transgenic expression of green fluorescent protein (GFP) reporter that recapitulates the spatial and temporal expression pattern of endogenous Tctex-1. This construct specifically targeted expression to the nestin+/Pax6+/GLAST+ radial glial cells and Tbr2+ intermediate progenitors when the reporter construct was delivered to developing mouse neocortex via in utero electroporation. Characterization of mice transgenically expressing GFP under the same regulatory element showed that the GFP expression is faithful to endogenous Tctex-1 at the subgranular zone (SGZ) of dentate gyrus, ventricular/subventricular zone of lateral ventricles, and ependymal layer of 3rd ventricle of adult brains. Immunolocalization and bromodeoxyuridine incorporation studies of adult SGZ in four independent mouse lines showed that Tctex-1:GFP reporter selectively marks nestin+/GFAP+/Sox2+ neural stem-like cells in two mouse lines (4 and 13). In two other mouse lines (17 and 18), Tctex-1:GFP is selectively expressed in Type-2 and Type-3 transient amplifying progenitors and a small subset of young neuronal progeny. The P/E-Tctex-1 reporter mouse studies independently confirmed the specific enrichment of Tctex-1 at adult SGZ stem/progenitor cells. Furthermore, these studies supported the notion that an analogous transcriptional program may be used to regulate neurogenesis in embryonic cerebral cortex and adult hippocampus. Finally, the genomic sequences and the reporter mouse lines described here provide useful experimental tools to advance adult neural stem cell research. J. Comp. Neurol. 518:3327,3342, 2010. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||