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ABSTRACT: The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair. Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors. Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells. To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments. Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus. It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction. We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair. Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48h and peaked at 7days. At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells. Interestingly, aromatase B expression was significantly reduced 48h and 7days after the injury, but surprisingly, at 72h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms. Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish. This article is part of a Special Issue entitled Hormones & Neurotrauma.
Hormones and Behavior 04/2012; · 3.87 Impact Factor
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ABSTRACT: The brain of adult teleost fish exhibits several unique and interesting features, notably an intense neurogenic activity linked to persistence of radial glial cells acting as neural progenitors, and a high aromatase activity supported by strong expression of the cyp19a1b gene. Strikingly, cyp19a1b expression is restricted to radial glial cells, suggesting that estrogens are able to modulate their activity. This raises the question of the origin, central or peripheral, of C19 androgens available for aromatization. This study aimed to investigate the activity and expression of other main steroidogenic enzymes in the brain of adult zebrafish. We demonstrate by high-performance liquid chromatography that the zebrafish brain has the ability to convert [³H]-pregnenolone into a variety of radiolabeled steroids such as 17OH-pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydro-testosterone, estrone, estradiol, progesterone, and dihydro- and tetrahydro-progesterone. Next, we show by in situ hybridization that messengers for key steroidogenic enzymes, such as Cyp11a1 (P450(SCC)), 3β-Hsd, Cyp17 and Cyp19a1b, are widely expressed in the forebrain where they exhibit an overall similar pattern. By combining aromatase B immunohistochemistry with in situ hybridization, we show that cyp11a1, 3β-hsd and cyp17 messengers are found in part in aromatase B-positive radial processes, suggesting mRNA export. This set of results provides the first demonstration that the brain of fish can produce true neurosteroids, possibly in radial glial cells. Given that radial glial cells are brain stem cells during the entire lifespan of fish, it is suggested that at least some of these neurosteroids are implicated in the persisting neurogenic process.
European Journal of Neuroscience 06/2011; 34(1):45-56. · 3.63 Impact Factor
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ABSTRACT: In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors. However, although synthesis of neuroprogestagens has been documented recently in the brain of zebrafish, information on the presence of progesterone receptors is very limited. In zebrafish, a single nuclear progesterone receptor (pgr) has been cloned and characterized. Here, we demonstrate that this pgr is widely distributed in all regions of the zebrafish brain. Interestingly, we show that Pgr is strongly expressed in radial glial cells and more weakly in neurons. Finally, we present evidence, based on quantitative PCR and immunohistochemistry, that nuclear progesterone receptor mRNA and proteins are upregulated by estrogens in the brain of adult zebrafish. These data document for the first time the finding that radial glial cells are preferential targets for peripheral progestagens and/or neuroprogestagens. Given the crucial roles of radial glial cells in adult neurogenesis, the potential effects of progestagens on their activity and the fate of daughter cells require thorough investigation.
PLoS ONE 01/2011; 6(11):e28375. · 4.09 Impact Factor
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ABSTRACT: Unlike that of mammals, the brain of adult teleost fish exhibits an intense and widespread neurogenic activity as a result of the persistence of radial glial cells acting as neural progenitors throughout life. Because chemokines, notably CXCL12, and their receptors, such as CXCR4, play key roles in mammalian embryonic neurogenesis, we investigated Cxcr4 and Cxcl12 expressions in the brain of adult zebrafish and their potential relationships with cell proliferation. Cxcr4 expression was found to be restricted to radial glial cells in the adult zebrafish, where it is co-expressed with established radial glial cell markers, such as brain lipid-binding protein (Blbp) or the estrogen-synthesizing enzyme aromatase B (Cyp19a1b). Double stainings combining proliferating cell nuclear antigen (PCNA) and Cxcr4 immunolabelling indicated that there is no obvious association between Cxcr4 expression and radial glial cell proliferation. Interestingly, cxcl12a messengers were detected in ventricular regions, in cells corresponding to aromatase B-immunoreactive radial glial cells. Altogether, our data demonstrate Cxcl12 and Cxcr4 expression in radial glial cells of the brain of adult zebrafish, supporting important roles for the Cxcl12/Cxcr4 pair in brain development and functioning.
The Journal of Comparative Neurology 12/2010; 518(24):4855-76. · 3.81 Impact Factor
