Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU) or in situ hybridizations for cell type markers (Vimentin, Sox2). We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA-) cells and not radial glial (Vimentin+) or progenitors (Sox2+) cells.
ISSN: 1932-6203

hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/file/The_Neurogenic_Factor-accepted.pdf
DOI : 10.1371/journal.pone.0066487

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Neurogenesis initiates during early development and it continues through later developmental stages and in adult animals to enable expansion, remodeling, and homeostasis of the nervous system. The generation of nerve cells has been analyzed in detail in few bilaterian model organisms, leaving open many questions about the evolution of this process. As the sister group to bilaterians, cnidarians occupy an informative phylogenetic position to address the early evolution of cellular and molecular aspects of neurogenesis and to understand common principles of neural development. Here we review studies in several cnidarian model systems that have revealed significant similarities and interesting differences compared to neurogenesis in bilaterian species, and between different cnidarian taxa. Cnidarian neurogenesis is currently best understood in the sea anemone Nematostella vectensis, where it includes epithelial neural progenitor cells that express transcription factors of the soxB and atonal families. Notch signaling regulates the number of these neural progenitor cells, achaete-scute and dmrt genes are required for their further development and Wnt and BMP signaling appear to be involved in the patterning of the nervous system. In contrast to many vertebrates and Drosophila, cnidarians have a high capacity to generate neurons throughout their lifetime and during regeneration. Utilizing this feature of cnidarian biology will likely allow gaining new insights into the similarities and differences of embryonic and regenerative neurogenesis. The use of different cnidarian model systems and their expanding experimental toolkits will thus continue to provide a better understanding of evolutionary and developmental aspects of nervous system formation.
ISSN: 1759-7692

Droits : http://creativecommons.org/licenses/by-nc/
hal-01405097
http://hal.upmc.fr/hal-01405097
http://hal.upmc.fr/hal-01405097/document
http://hal.upmc.fr/hal-01405097/file/Rentzsch_et_al-2016-Wiley_Interdisciplinary_Reviews__Developmental_Biology.pdf
DOI : 10.1002/wdev.257

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis. Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed
ISSN: 0960-0760

hal-01174214
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174214/file/Steroid%20modulation%20of%20neurogenesis.pdf
DOI : 10.1016/j.jsbmb.2015.06.011

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
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 48 h and peaked at 7 days. 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 48 h and 7 days after the injury, but surprisingly, at 72 h 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.
ISSN: 0018-506X

inserm-00831715
http://www.hal.inserm.fr/inserm-00831715
DOI : 10.1016/j.yhbeh.2012.04.003
PUBMED : 22521210

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Adult fish exhibit a strong neurogenic capacity due to the persistence of radial glial progenitor cells. In zebrafish, radial glial cells display well-established markers such as the estrogen-synthesizing enzyme (AroB) and the brain lipid binding protein (Blbp), which is known to strongly bind omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). While Blpb is mainly described in the telencephalon of adult zebrafish, its expression in the remaining regions of the brain is poorly documented. The present study was designed to further investigate Blbp expression in the brain, its co-expression with AroB, and its link with radial glial cells proliferation in zebrafish. We generated a complete and detailed mapping of Blbp expression in the whole brain and show its complete co-expression with AroB, except in some tectal and hypothalamic regions. By performing PCNA and Blbp immunohistochemistry on cyp19a1b-GFP (AroB-GFP) fish, we also demonstrated preferential Blbp expression in proliferative radial glial cells in almost all regions studied. To our knowledge, this is the first complete and detailed mapping of Blbp-expressing cells showing strong association between Blbp and radial glial cell proliferation in the adult brain of fish. Given that zebrafish is now recognized models for studying neurogenesis and brain repair, our data provide detailed characterization of Blbp in the entire brain and open up a broad field of research investigating the role of omega-3 polyunsaturated fatty acids in neural stem cell activity in fish
ISSN: 1567-133X

hal-01237088
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237088
DOI : 10.1016/j.gep.2015.11.003
PUBMED : 26611722

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations.
ISSN: 1932-6203

hal-01359562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359562
DOI : 10.1371/journal.pone.0158057
PUBMED : 27336917

Éditeur(s) : HAL CCSD
Résumé : International audience
Estrogens affect brain development of vertebrates, not only by impacting activity and morphology of existing circuits, but also by modulating embryonic and adult neurogenesis. The issue is complex as estrogens can not only originate from peripheral tissues, but also be locally produced within the brain itself due to local aromatization of androgens. In this respect, teleost fishes are quite unique because aromatase is expressed exclusively in radial glial cells, which represent pluripotent cells in the brain of all vertebrates. Expression of aromatase in the brain of fish is also strongly stimulated by estrogens and some androgens. This creates a very intriguing positive auto-regulatory loop leading to dramatic aromatase expression in sexually mature fish with elevated levels of circulating steroids. Looking at the effects of estrogens or anti-estrogens in the brain of adult zebrafish showed that estrogens inhibit rather than stimulate cell proliferation and newborn cell migration. The functional meaning of these observations is still unclear, but these data suggest that the brain of fish is experiencing constant remodeling under the influence of circulating steroids and brain-derived neurosteroids, possibly permitting a diversification of sexual strategies, notably hermaphroditism. Recent data in frogs indicate that aromatase expression is limited to neurons and do not concern radial glial cells. Thus, until now, there is no other example of vertebrates in which radial progenitors express aromatase. This raises the question of when and why these new features were gained and what are their adaptive benefits. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Droits : info:eu-repo/semantics/OpenAccess
hal-01102449
https://hal.archives-ouvertes.fr/hal-01102449
https://hal.archives-ouvertes.fr/hal-01102449/document
https://hal.archives-ouvertes.fr/hal-01102449/file/Coumailleau%20et%20al%20final%20manuscript.pdf
DOI : 10.1016/j.bbagrm.2014.07.002

Éditeur(s) : HAL CCSD
Résumé : International audience
Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the hippocampus of pre-adolescent offspring.
Psychoneuroendocrinology

hal-01579611
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579611
DOI : 10.1016/j.psyneuen.2017.07.480
PUBMED : 28735226

Éditeur(s) : HAL CCSD Oxford Scholarship Online
Résumé : Brain aromatase in fish is an exciting research topic because of several unconventional features that challenge the established view based on studies in other vertebrates. First, the brain of teleost fish exhibits a high degree of aromatase activity, especially in sexually mature animals. Given the emerging roles of estrogens in neurogenesis, the unique features of the adult fish brain suggest that, in addition to classical functions on brain sexual differentiation and sexual behavior, aromatase expression in radial glial cells could be involved in the modulation of the high proliferative activity in the brain of fish.
Brain Aromatase, Estrogens, and Behavior

ISBN : 9780199841196
hal-00905522
https://hal.archives-ouvertes.fr/hal-00905522
DOI : 10.1093/acprof:oso/9780199841196.003.0007

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning. © 2015 Wiley Periodicals, Inc. Dev Psychobiol
ISSN: 0012-1630

hal-01237091
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237091
DOI : 10.1002/dev.21372
PUBMED : 26477449

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.
ISSN: 0041-008X

hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01558816/file/Lecomte%20et%20al.%20-%20Assessment%20of%20the%20potential%20activity%20of%20major%20diet.pdf
DOI : 10.1016/j.taap.2017.04.005