Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice

Brandt, Moritz; Jessberger, Sebastian; Steiner, Barbara; Kronenberg, Golo; Reuter, Katja; Bick-Sander, Anika; Behrens, Wolfger von der; Kempermann, Gerd

doi:10.1016/s1044-7431(03)00207-0

Cited by 454 publications

(484 citation statements)

References 47 publications

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“…The adult-born calretininexpressing neurons (5) most closely match the "class 4" calretinin-expressing cells of Gabbott et al (33). Interestingly, new granule cells in the adult dentate gyrus initially express calretinin before switching to calbindin expression (34), suggesting that new calretinin-and calbindinexpressing neocortical interneurons could potentially represent a single interneuron subtype at different maturational stages.…”

Section: New Neurons In the Adult Brain Are Interneuronsmentioning

confidence: 55%

New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?

Cameron

Dayer²

2008

Biological Psychiatry

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During the last decade, the intense study of adult hippocampal neurogenesis has led to several new lines of inquiry in the field of psychiatry. Although it is generally believed that adult mammalian neurogenesis is restricted to the hippocampus and olfactory bulb, a growing number of studies have described new neurons in the adult neocortex in both rodents and non-human primates. Interestingly, all of the new neurons observed in these studies have features of interneurons rather than pyramidal cells, the largest neuronal population of the neocortex. In this review, we discuss features of these interneurons that could help to explain why cortical neurogenesis has been so difficult to detect. In addition, these features suggest ways that production of even a small numbers of new neurons in the adult cortex could make a significant impact on neocortical function.It is widely accepted that adult neurogenesis occurs in two mammalian brain regions: the dentate gyrus and olfactory bulb. Interestingly, the earliest reports of adult neurogenesis in these two regions also described new neurons in the adult neocortex (1;2). These early neocortical neurogenesis findings have been replicated in recent studies (3-7), but the existence of adult neurogenesis in the neocortex remains controversial, largely due to the existence of negative reports. In non-human primates, new neurons have been reported in prefrontal, inferior temporal, and posterior parietal cortex (3;6;7), though other groups have found no new neurons in the neocortex of adult primates, including humans (8-11). In adult rodents, studies have reported finding new neurons in the anterior neocortex (5;7;12), but others found no new neocortical neurons in enriched, electroconvulsive seizure-treated, or control conditions (13; 14). Several additional studies have reported finding new neurons in the neocortex only after ischemia or targeted neuronal death (15-18). These contradictory findings are difficult to reconcile, because all of the studies of adult neurogenesis in the neocortex carried out within the past ten years have used essentially the same methods: injection and immunohistochemical detection of the S-phase marker bromodeoxyuridine (BrdU) to mark newly-born cells combined with immunohistochemistry for neuronal markers to determine whether the new cells are neurons. Virtually all positive and negative studies have used the neuron-specific marker NeuN (Neuronal Nuclei) to identify BrdU-labeled cells as mature neurons, and BrdUlabeled neurons in the adult rat neocortex have recently been characterized with several additional neuronal markers as well (5). The remainder of this review will describe features of new cortical neurons suggesting that they are interneurons rather than pyramidal neurons; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review o...

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Section: New Neurons In the Adult Brain Are Interneuronsmentioning

confidence: 55%

New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?

Cameron

Dayer²

2008

Biological Psychiatry

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“…They cease to express PSA-NCAM and Dcx but express Prox-1, ␤III-tubulin, NeuN, and markers of mature granule neurons (e.g., calbindin; ref. 25).…”

Section: Resultsmentioning

confidence: 99%

Fluoxetine targets early progenitor cells in the adult brain

Encinas

Vaahtokari

Enikolopov

2006

Proc. Natl. Acad. Sci. U.S.A.

566

529

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Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neurogenic agents in these distinct subclasses of neuronal precursors. We use this line to demonstrate that the selective serotonin reuptake inhibitor antidepressant fluoxetine does not affect division of stem-like cells in the dentate gyrus but increases symmetric divisions of an early progenitor cell class. We further demonstrate that these cells are the sole class of neuronal progenitors targeted by fluoxetine in the adult brain and suggest that the fluoxetine-induced increase in new neurons arises as a result of the expansion of this cell class. This finding defines a cellular target for antidepressant drug therapies.hippocampus ͉ neural stem cells ͉ neurogenesis ͉ dentate gyrus ͉ antidepressants A ntidepressant drugs of the selective serotonin reuptake inhibitor (SSRI) class (e.g., fluoxetine) are commonly used to treat a wide spectrum of mood disorders in adults (1); they also are increasingly prescribed to children and adolescents (2, 3). However, the cellular basis for the action of SSRIs is not clear. In addition to its effects on neurotransmission, SSRI fluoxetine increases generation of new neurons in the dentate gyrus (DG) of the adult brain (4-9). Importantly, recent findings suggest that this increase may be a causative factor in the behavioral effects of this class of antidepressants (7). These discoveries may provide a novel framework for understanding depression and designing new therapeutic drugs. However, the step within the neuronal differentiation cascade targeted by SSRIs remains unknown. Particular targets (e.g., stem cells vs. early progenitors vs. advanced neuroblasts) may imply different molecular mechanisms of controlling cell division and survival, different circuits affected by the drugs, and different insights on the behavioral action of the drugs.One of the problems in defining SSRI targets within the neuronal proliferation-differentiation cascade is the imprecision in quantifying the changes in each class of neural precursor cells in the brain. Accurate enumeration of changes in distinct subpopulations of neuronal precursors by immunocytochemistry is problematic: High cell density, complex cell morphology, and uncertainties in defining distinct boundaries between subclasses of cells reduces the precision of evaluating changes in particular subclasses of neuronal precursors (e.g., in contrast to BrdU or thymidine labeling of cell nuclei, where great precision can be achieved); this problem is particularly acute in the young brain, where the number of neural stem and progenitor cells is particularly ...

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“…Prox 1 is a transcription factor allowing the detection of new granule neurons in the DG (Pleasure et al, 2000;Brandt et al, 2003). Double labeling was performed with Alexa Fluor 488-and 546-goat and rabbit antibodies (1 : 1000, Molecular Probes).…”

Section: Hippocampal Primary Culture and Morphometric Analysesmentioning

confidence: 99%

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Soumier¹,

Banasr²,

Lortet³

et al. 2009

Neuropsychopharmacol

145

138

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Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT 2C ) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3b) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT 2C ) antagonist properties, we determined whether melatonin and 5-HT 2C receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT 2C receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT 2C receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT 2C antagonism may be involved in promotion by agomelatine of survival in the hippocampus.

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Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice

Cited by 454 publications

References 47 publications

New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?

New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?

Fluoxetine targets early progenitor cells in the adult brain

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

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