Adult Mammalian Brain (adult + mammalian_brain)

Distribution by Scientific Domains


Selected Abstracts


Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2010
Anna 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]


Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009
Claudio Giachino
Abstract The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreERT2 allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreERT2 -expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreERT2 -expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreERT2 -targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB. [source]


Doublecortin as a marker of adult neuroplasticity in the canary song control nucleus HVC

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008
Jacques Balthazart
Abstract It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn neurons. In the developing and adult mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic neurons and, as a part of the microtubule machinery, required for neuronal migration. We recently showed that in adult canaries, DCX-immunoreactive (ir) cells are present throughout the telencephalon, but the link between DCX and the active neurogenesis observed in songbirds remained uncertain. We demonstrate here that DCX labels recently born cells in the canary telencephalon and that, in parallel with changes in HVC volume, the number of DCX-ir cells is increased specifically in the HVC of testosterone-treated males compared with castrates, and in castrated testosterone-treated males paired with a female as compared with males paired with another male. The numbers of elongated DCX-ir cells (presumptive migrating neurons) and round multipolar DCX-ir cells (differentiating neurons) were also affected by the sex of the subjects and their photoperiodic condition (photosensitive vs photostimulated vs photorefractory). Thus, in canaries the endocrine state, as well as the social or photoperiodic condition independently of variation in steroid hormone action, affects the number of cells expressing a protein involved in neuronal migration specifically in brain areas that incorporate new neurons in the telencephalon. The DCX gene may be one of the targets by which testosterone and social stimuli induce seasonal changes in the volume of song nuclei. [source]


Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007
Yasuhisa Tamura
Abstract In the adult mammalian brain, multipotent stem or progenitor cells involved in reproduction of neurons and glial cells have been well investigated only in very restricted regions; the subventricular zone of the lateral ventricle and the dentate gyrus in the hippocampal formation. In the neocortex, a series of in vitro studies has suggested the possible existence of neural progenitor cells possessing neurogenic and/or gliogenic potential in adult mammals. However, the cellular properties of the cortical progenitor cells in vivo have not been fully elucidated. Using 5,-bromodeoxyuridine labeling and immunohistochemical analysis of cell differentiation markers, we found that a subpopulation of NG2-immunopositive cells co-expressing doublecortin (DCX), an immature neuron marker, ubiquitously reside in the adult rat neocortex. Furthermore, these cells are the major population of proliferating cells in the region. The DCX(+)/NG2(+) cells reproduced the same daughter cells, or differentiated into DCX(+)/NG2(,) (approximately 1%) or DCX(,)/NG2(+) (approximately 10%) cells within 2 weeks after cell division. The DCX(+)/NG2(,) cells were also immunopositive for TUC-4, a neuronal linage marker, suggesting that these cells were committed to neuronal cell differentiation, whereas the DCX(,)/NG2(+) cells showed faint immunoreactivity for glutathione S-transferase (GST)-pi, an oligodendrocyte lineage marker, in the cytoplasm, suggesting glial cell lineage, and thereafter the cells differentiated into NG2(,)/GST-pi(+) mature oligodendrocytes after a further 2 weeks. These findings indicate that DCX(+)/NG2(+) cells ubiquitously exist as ,multipotent progenitor cells' in the neocortex of adult rats. [source]


Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesis

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005
Sunayana B. Banerjee
Abstract Electroconvulsive seizure (ECS) induces structural remodelling in the adult mammalian brain, including an increase in adult hippocampal neurogenesis. The molecular mechanisms that underlie this increase in the proliferation of adult hippocampal progenitors are at present not well understood. We hypothesized that ECS may recruit the Sonic hedgehog (Shh) pathway to mediate its effects on adult hippocampal neurogenesis, as Shh is known to enhance the proliferation of neuronal progenitors and is expressed in the adult basal forebrain, a region that sends robust projections to the hippocampus. Here we demonstrate that the ECS-induced increase in proliferation of adult hippocampal progenitors was completely blocked in animals treated with cyclopamine, a pharmacological inhibitor of Shh signalling. Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus, as we observed a robust upregulation of Patched (Ptc) mRNA, a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling. This increase was rapid and restricted to the dentate gyrus, where the adult hippocampal progenitors reside. In addition, both acute and chronic ECS decreased Smoothened (Smo) mRNA, the other component of the Shh receptor complex, selectively within the dentate gyrus. However, ECS did not appear to influence Shh expression within the basal forebrain, the site from which it has been suggested to be anterogradely transported to the hippocampus. Together, our findings demonstrate that ECS regulates the Shh signalling cascade and indicate that the Shh pathway may be an important mechanism through which ECS enhances adult hippocampal neurogenesis. [source]


Dopamine and adult neurogenesis

JOURNAL OF NEUROCHEMISTRY, Issue 3 2007
Andreas Borta
Abstract Dopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we approach a highly controversial question: can the adult human brain use neurogenesis to replace the dopaminergic neurones in the substantia nigra that are lost in Parkinson's disease? [source]


Subcellular segregation of distinct heteromeric NMDA glutamate receptors in the striatum

JOURNAL OF NEUROCHEMISTRY, Issue 4 2003
Anthone W. Dunah
Abstract Functional N -methyl- d -aspartate (NMDA) glutamate receptors are composed of heteromeric complexes of NR1, the obligatory subunit for channel activity, and NR2 or NR3 family members, which confer variability in the properties of the receptors. Recent studies have provided evidence for the existence of both binary (containing NR1 and either NR2A or NR2B) and ternary (containing NR1, NR2A, and NR2B) receptor complexes in the adult mammalian brain. However, the mechanisms regulating subunit assembly and receptor localization are not well understood. In the CNS, NMDA subunits are present both at intracellular sites and the post-synaptic membrane of neurons. Using biochemical protein fractionation and co-immunoprecipitation approaches we have found that in rat striatum binary NMDA receptors are widely distributed, and can be identified in the light membrane, synaptosomal membrane, and synaptic vesicle-enriched subcellular compartments. In contrast, ternary receptors are found exclusively in the synaptosomal membranes. When striatal proteins are chemically cross-linked prior to subcellular fractionation, ternary NMDA receptors can be precipitated from the light membrane and synaptic vesicle-enriched fractions where this type of receptor complex is not detectable under normal conditions. These findings suggest differential targeting of distinct types of NMDA receptor assemblies between intracellular and post-synaptic sites based on subunit composition. This targeting may underlie important differences in the regulation of the transport pathways involved in both normal as well as pathological receptor functions. [source]


Disruption of neurogenesis by amyloid ,-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Norman J. Haughey
Abstract Neurogenesis occurs in the adult mammalian brain and may play roles in learning and memory processes and recovery from injury, suggesting that abnormalities in neural progenitor cells (NPC) might contribute to the pathogenesis of disorders of learning and memory in humans. The objectives of this study were to determine whether NPC proliferation, survival and neuronal differentiation are impaired in a transgenic mouse model of Alzheimer's disease (AD), and to determine the effects of the pathogenic form of amyloid ,-peptide (A,) on the survival and neuronal differentiation of cultured NPC. The proliferation and survival of NPC in the dentate gyrus of the hippocampus was reduced in mice transgenic for a mutated form of amyloid precursor protein that causes early onset familial AD. A, impaired the proliferation and neuronal differentiation of cultured human and rodent NPC, and promoted apoptosis of neuron-restricted NPC by a mechanism involving dysregulation of cellular calcium homeostasis and the activation of calpains and caspases. Adverse effects of A, on NPC may contribute to the depletion of neurons and cognitive impairment in AD. [source]


Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2009
Caixin Su
Abstract Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) caused by an abnormal rate of apoptosis. Endogenous stem cells in the adult mammalian brain indicate an innate potential for regeneration and possible resource for neuroregeneration in PD. We previously showed that guanosine prevents apoptosis even when administered 48 hr after the toxin 1-methyl-4-phenylpyridinium (MPP+). Here, we induced parkinsonism in rats with a proteasome inhibitor. Guanosine treatment reduced apoptosis, increased tyrosine hydroxylase,positive dopaminergic neurons and expression of tyrosine hydroxylase in the SNc, increased cellular proliferation in the SNc and subventricular zone, and ameliorated symptoms. Proliferating cells in the subventricular zone were nestin-positive adult neural progenitor/stem cells. Fibroblast growth factor-2-expressing cells were also increased by guanosine. Thus, guanosine protected cells from apoptosis and stimulated "intrinsic" adult progenitor/stem cells to become dopaminergic neurons in rats with proteasome inhibitor,induced PD. The cellular/molecular mechanisms underlying these effects may open new avenues for development of novel therapeutics for PD. 2008 Wiley-Liss, Inc. [source]


Hepatocyte growth factor stimulates cell motility in cultures of the striatal progenitor cells ST14A

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003
E. Cacci
Abstract Hepatocyte growth factor/scatter factor (HGF/SF) is a growth factor with pleiotropic effects on different cell types. It acts as a mitogen and motility factor for many epithelial cells. HGF/SF and its receptor Met are present in the developing and adult mammalian brain and control neuritogenesis of sympathetic and sensory neurons. We report that the striatal progenitor ST14A cells express the Met receptor, which is activated after binding with HGF/SF. The interaction between Met and HGF/SF triggers a signaling cascade that leads to increased levels of c-Jun, c-Fos, and Egr-1 proteins, in agreement with data reported on the signaling events evoked by HGF in other cellular types. We also studied the effects of the exposure of ST14A cells to HGF/SF. By time-lapse photography, we observed that a 24-hr treatment with 50 ng/ml HGF/SF induced modification in cell morphology, with a decrease in cell-cell interactions and increase of cell motility. In contrast, no effect on cell proliferation was observed. To investigate which intracellular pathway is primarily involved we used PD98059 and LY294002, two specific inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAP-kinase/ERK-kinase) and phosphoinositide 3-OH kinase (PI3-K), respectively. Cell motility in HGF/SF treated cultures was inhibited by LY294002 but not by PD98059, suggesting that PI3-K plays a key role in mediating the HGF/SF-induced dissociation of ST14A cells. Previous evidence of HGF stimulation of motility in nervous system has been obtained on postmitotic neurons, which have already acquired their specificity. Data reported here of a motogenic response of ST14A cell line, which displays properties of neuronal progenitors, seem of interest because they suggest that HGF could play a role in very early steps of neurogenesis. 2003 Wiley-Liss, Inc. [source]


Proliferation and neurogenesis of neural stem cells enhanced by cerebral microvascular endothelial cells

MICROSURGERY, Issue 1 2008
Ying Guo M.D.
In adult mammalian brain, vascular cells reside throughout life, close to central nervous system germinal zones, and neural stem cells (NSCs) mainly localize in the dentate gyrus of the hippocampus, subventricular zone, and olfactory bulb. Microvessels appear to produce a special microenvironment that may influence the characteristics of NSCs. To explore this potential correlation, an in vitro model with cocultured cerebral microvascular endothelial cells (CMECs) and NSCs was established in our study by using a transwell coculture system. The expression of nestin and NF in the early stage of coculture, and NF in the late stage, was detected by immunostaining. The results demonstrated that CMECs can stimulate self-renewal of NSCs and inhibit their differentiation, implying the potential of CMECs in promoting the neural differentiation of NSCs. 2007 Wiley-Liss, Inc. Microsurgery, 2008. [source]


Expression of PTPRO in the interneurons of adult mouse olfactory bulb

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2010
Takenori Kotani
PTPRO is a receptor-type protein tyrosine phosphatase (PTP) with a single catalytic domain in its cytoplasmic region and multiple fibronectin type III-like domains in its extracellular region. In the chick, PTPRO mRNA has been shown to be particularly abundant in embryonic brain, and PTPRO is implicated in axon growth and guidance during embryonic development. However, the temporal and spatial expression of PTPRO protein in the mammalian CNS, particularly in the juvenile and adult mammalian brain, has not been evaluated in any detail. By immunohistofluorescence analysis with a monoclonal antibody to PTPRO, we show that PTPRO is widely expressed throughout the mouse brain from embryonic day 16 to postnatal day 1, while expression is largely confined to the olfactory bulb (OB) and olfactory tubercle in the adult brain. In the OB, PTPRO protein is expressed predominantly in the external plexiform layer, the granule cell layer, and the glomerular layer (GL). In these regions, expression of PTPRO is predominant in interneurons such as ,-aminobutyric acid (GABA)-ergic or calretinin (CR)-positive granule cells. In addition, PTPRO is expressed in GABAergic, CR-positive, tyrosine hydroxylase-positive, or neurocalcin-positive periglomerular cells in the GL. Costaining of PTPRO with other neuronal markers suggests that PTPRO is likely to be localized to the dendrites or dendritic spines of these olfactory interneurons. Thus, PTPRO might participate in regulation of dendritic morphology or synapse formation of interneurons in the adult mouse OB. J. Comp. Neurol. 518:119,136, 2010. 2009 Wiley-Liss, Inc. [source]


Expression of PTPRO in the interneurons of adult mouse olfactory bulb

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2010
Takenori Kotani
Abstract PTPRO is a receptor-type protein tyrosine phosphatase (PTP) with a single catalytic domain in its cytoplasmic region and multiple fibronectin type III-like domains in its extracellular region. In the chick, PTPRO mRNA has been shown to be particularly abundant in embryonic brain, and PTPRO is implicated in axon growth and guidance during embryonic development. However, the temporal and spatial expression of PTPRO protein in the mammalian CNS, particularly in the juvenile and adult mammalian brain, has not been evaluated in any detail. By immunohistofluorescence analysis with a monoclonal antibody to PTPRO, we show that PTPRO is widely expressed throughout the mouse brain from embryonic day 16 to postnatal day 1, while expression is largely confined to the olfactory bulb (OB) and olfactory tubercle in the adult brain. In the OB, PTPRO protein is expressed predominantly in the external plexiform layer, the granule cell layer, and the glomerular layer (GL). In these regions, expression of PTPRO is predominant in interneurons such as ,-aminobutyric acid (GABA)-ergic or calretinin (CR)-positive granule cells. In addition, PTPRO is expressed in GABAergic, CR-positive, tyrosine hydroxylase-positive, or neurocalcin-positive periglomerular cells in the GL. Costaining of PTPRO with other neuronal markers suggests that PTPRO is likely to be localized to the dendrites or dendritic spines of these olfactory interneurons. Thus, PTPRO might participate in regulation of dendritic morphology or synapse formation of interneurons in the adult mouse OB. J. Comp. Neurol. 518:119,136, 2010. 2009 Wiley-Liss, Inc. [source]


Adult neural stem cells and their role in brain pathology,

THE JOURNAL OF PATHOLOGY, Issue 2 2009
G Yadirgi
Abstract Stem cells are multipotent cells that can give rise to a differentiated progeny as well as self-renew. The balanced coordination of these two stem cell fates is essential for embryonic development and tissue homeostasis in the adult. Perturbed stem cell function contributes significantly to a variety of pathological conditions, eg impaired self-renewal capacity due to cellular senescence contributes to ageing, and degenerative diseases or impaired stem cell differentiation by oncogenic mutations contribute to cancer formation. This review focuses on the molecular mechanisms involved in regulating the normal function of neural stem cells in the adult mammalian brain and on the involvement of these cells in brain pathology. Copyright 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]