Éditeur(s) : HAL CCSD Frontiers
Résumé : International audience
Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA). The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4- or 7-day post-fertilization (dpf) zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B), expressed in the brain, using three different in situ/in vivo strategies: (1) Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols; (2) Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus); and (3) Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay) at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF, or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα). Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP) did not show estrogenic activity in our model
ISSN: 1662-4548

hal-01299976
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01299976
PUBMED : 27047331
DOI : 10.3389/fnins.2016.00112
PUBMEDCENTRAL : PMC4805609

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : Loin d’être un phénomène nouveau, les mobilités internationales se sont fortement accrues depuis les années 1960. Aujourd’hui, le contexte de mondialisation tend à accélérer les dynamiques migratoires alors que dans le même temps s’observe une élévation des niveaux d’éducation. Ainsi, la soutenabilité de l’augmentation de la fuite des cerveaux dans le monde soulève interrogations et réflexions.Le poids des flux de migrants qualifiés allié à la fragilité relative des données, pose la nécessité d’aborder en profondeur le problème de la fuite des cerveaux. Une analyse au cas par cas s’impose. À partir de données se rapportant à la diaspora caribéenne sur la base statistique de Docquier et Marfouk, cet article propose une réflexion sur les facteurs explicatifs de la fuite des cerveaux dans les territoires insulaires caribéens.
Far from being a new phenomenon, the international motilities have increased since the 60’s. Today, the context of globalization tends to accelerate the migratory dynamics while at the same time observed a rise of the educational levels. The increase of the brain drain has respite to many questions.Nevertheless, image, nature of flows of skilled migrants combined with relative data’s fragility and the necessity to approach the problem and presenting appropriate policies, impose an analysis case by case. Using data relating to the Caribbean diaspora on the statistical basis of Docquier and Marfouk, this article purpose a reflection on the factors that explain the brain drain in the Caribbean islands.
Caraïbes

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.4702
http://journals.openedition.org/etudescaribeennes/4702

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides (n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines (n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds (n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.
ISSN: 1660-4601

hal-01560242
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560242
PUBMED : 28665355
DOI : 10.3390/ijerph14070708

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
UNLABELLED: ABSTRACT: BACKGROUND: Genomics, transcriptomics and proteomics of glioblastoma multiforme (GBM) have recently emerged as possible tools to discover therapeutic targets and biomarkers for new therapies including immunotherapy. It is well known that macroscopically complete surgical excision, radiotherapy and chemotherapy have therapeutic limitations to improve survival in these patients. In this study, we used a differential proteomic-based technique (2D-Difference Gel Electrophoresis) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify proteins that may serve as brain tumor antigens in new therapeutic assays. Five samples of patients presenting a GBM and five samples of microscopically normal brain tissues derived from brain epileptic surgery specimen were labeled and run in 2D-PAGE (Two-Dimensional Polyacrylamide Gel Electrophoresis) with an internal pool sample on each gel. Five gels were matched and compared with DIA (Difference In-gel Analysis) software. Differential spots were picked, in-gel digested and peptide mass fingerprints were obtained. RESULTS: From 51 protein-spots significantly up-regulated in GBM samples, mass spectrometry (MS) identified twenty-two proteins. The differential expression of a selected protein set was first validated by western-blotting, then tested on large cohorts of GBM specimens and non-tumor tissues, using immunohistochemistry and real-time RT-PCR. CONCLUSIONS: Our results confirmed the importance of previously described proteins in glioma pathology and their potential usefulness as biological markers but also revealed some new interesting targets for future therapies.
ISSN: 1477-5956

inserm-00585020
http://www.hal.inserm.fr/inserm-00585020
http://www.hal.inserm.fr/inserm-00585020/document
http://www.hal.inserm.fr/inserm-00585020/file/1477-5956-9-16.pdf
DOI : 10.1186/1477-5956-9-16

Éditeur(s) : HAL CCSD Elsevier - International Brain Research Organization
Résumé : International audience
Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the CG2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain
ISSN: 0306-4522

hal-01301509
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01301509
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01301509/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01301509/file/Gestational%20stress%20and%20fluoxetine%20treatment%20%281%29.pdf
PUBMED : 27060483

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Coronaviruses (CoVs) have shown neuroinvasive properties in human and animal secondary to replication in peripheral organ but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood brain barrier (BBB). Using the high hepatotropic mouse hepatitis virus (MHV) type 3, its attenuated variant 51.6-MHV3, showing low tropism for endothelial cells, and the low hepatotropic MHV-A59 strains from murine coronavirus group, we investigated the viral-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was only observed in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of ZO-1, VE-cadherin and occludin but not claudin-5 in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective IFN-β production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain. IMPORTANCE: Coronaviruses (CoVs) infect several mammals including humans and are associated with respiratory, gastrointestinal and/or neurological diseases. Some evidences suggest that human respiratory CoVs may show neuroinvasive properties. Indeed, the SARS-CoV, causing severe acute respiratory syndrome, and the CoVs OC43 and 229E were found in the brains of SARS and multiple sclerosis patients respectively. These finding suggest that hematogenous spread CoVs may gain access to CNS at the BBB level. Herein we report for the first time that CoVs exhibit ability to cross the BBB according to strain virulence. BBB invasion by CoVs correlates with viral-induced disruption of tight junctions on BMECs, leading to BBB dysfunction and enhanced permeability. We provide evidence that production of IFN-β by BMECs during CoV infection may prevent BBB breakdown and brain viral invasion
ISSN: 0022-538X

hal-01187308
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187308
DOI : 10.1128/JVI.01501-15
PUBMED : 26202229

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
PURPOSE: Two hundred and fifty-three patients were included in a study on the etiology of encephalitis, carried out in France in 2007. Tuberculosis was the second most frequently identified cause, after HSV and with the same number of cases as VZV. The authors report the specific features of patients presenting with tuberculosis encephalitis (TE). METHODS: TE patients were defined as patients presenting with encephalitis, with positive culture or PCR for Mycobacterium tuberculosis, or the association of clinical, biological, imaging, and epidemiological evidence (possible cases). Clinical, microbiological, and brain imaging data was analyzed and compared to that of other included patients. RESULTS: Twenty cases of TE were identified. The M/F sex-ratio was 1.5, the mean age 53 years. Four (20%) patients had a history of tuberculosis before the encephalitis. The median delay between the onset of general and neurological symptoms was significantly longer for tuberculosis cases than for others (10 days vs. 2; P<10(-10)). The median CSF protein level was significantly higher for tuberculosis cases (2.1 g/L vs. 0.8 g/L, P=0.002). CT scan and MRI were normal on admission for eight patients out of 17. Fourteen isolated strains of M. tuberculosis were susceptible to first-line anti-tuberculosis drugs and one was rifampicin-resistant. Six (33%) patients died during hospitalization and two were lost to follow-up. Ten out of 12 (78.6%) had persisting neurological symptoms on discharge. DISCUSSION: Despite non-multiresistant MT strains, the case fatality rate among TE patients was high in our series. Early brain imaging is poor contributive for the diagnosis of TE.
ISSN: 0399-077X

hal-00874835
https://hal.archives-ouvertes.fr/hal-00874835
DOI : 10.1016/j.medmal.2013.05.003
PUBMED : 23816146

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
IntroductionFever is associated with a poor outcome in severely brain-injured patients, and its control is one of the therapies used in this condition. But, fever suppression may promote infection, and severely brain-injured patients are frequently exposed to infectious diseases, particularly ventilator-associated pneumonia (VAP). Therefore, we designed a study to explore the role of a fever control protocol in VAP development during neuro-intensive care.MethodsAn observational study was performed on severely brain-injured patients hospitalized in a university ICU. The primary goal was to assess whether fever control was a risk factor for VAP in a prospective cohort in which a fever control protocol was applied and in a historical control group. Moreover, the density of VAP incidence was compared between the two groups. The statistical analysis was based on a competing risk model multivariate analysis.ResultsThe study included 189 brain-injured patients (intervention group, n¿=¿98, and historical control group, n¿=¿91). The use of a fever control protocol was an independent risk factor for VAP (hazard ratio 2.73, 95% confidence interval [1.38, 5.38; P¿=¿0.005]). There was a significant increase in the incidence of VAP in patients treated with a fever control protocol (26.1 versus 12.5 VAP cases per 1000 days of mechanical ventilation). In cases in which a fever control protocol was applied for >3 days, we observed a higher rate of VAP in comparison with the rate among patients treated for ¿3 days.ConclusionFever control in brain-injured patients was a major risk factor for VAP occurrence, particularly when applied for >3 days.
ISSN: 1364-8535

hal-01118640
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118640
PUBMED : 25498970
DOI : 10.1186/s13054-014-0689-4
PUBMEDCENTRAL : PMC4279880

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 Public Library of Science
Résumé : International audience
Ghrelin is a gut-brain peptide hormone, which binds to the growth hormone secretagogue receptor (GHS-R) to regulate a wide variety of biological processes in fish. Despite these prominent physiological roles, no studies have reported the anatomical distribution of preproghrelin transcripts using in situ hybridization in a non-mammalian vertebrate, and its mapping within the different encephalic areas remains unknown. Similarly, no information is available on the possible 24-h variations in the expression of preproghrelin and its receptor in any vertebrate species. The first aim of this study was to investigate the anatomical distribution of ghrelin and GHS-R1a ghrelin receptor subtype in brain and gastrointestinal tract of goldfish (Carassius auratus) using immunohistochemistry and in situ hybridization. Our second aim was to characterize possible daily variations of preproghrelin and ghs-r1 mRNA expression in central and peripheral tissues using real-time reverse transcription-quantitative PCR. Results show ghrelin expression and immunoreactivity in the gastrointestinal tract, with the most abundant signal observed in the mucosal epithelium. These are in agreement with previous findings on mucosal cells as the primary synthesizing site of ghrelin in goldfish. Ghrelin receptor was observed mainly in the hypothalamus with low expression in telencephalon, pineal and cerebellum, and in the same gastrointestinal areas as ghrelin. Daily rhythms in mRNA expression were found for preproghrelin and ghs-r1 in hypothalamus and pituitary with the acrophase occurring at nighttime. Preproghrelin, but not ghs-r1a, displayed a similar daily expression rhythm in the gastrointestinal tract with an amplitude 3-fold higher than the rest of tissues. Together, these results described for the first time in fish the mapping of preproghrelin and ghrelin receptor ghs-r1a in brain and gastrointestinal tract of goldfish, and provide the first evidence for a daily regulation of both genes expression in such locations, suggesting a possible connection between the ghrelinergic and circadian systems in teleosts
ISSN: 1932-6203

hal-01225511
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225511
DOI : 10.1371/journal.pone.0141043
PUBMED : 26506093

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
ISSN: 0028-3908

hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/file/Gemmel%20-%20Perinatal%20fluoxetine%20prevents%20the%20effect.pdf
DOI : 10.1016/j.neuropharm.2017.10.009

Éditeur(s) : HAL CCSD Frontiers
Résumé : International audience
Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.
ISSN: 1662-5153

hal-01121829
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121829
PUBMED : 25477793
DOI : 10.3389/fnbeh.2014.00390
PUBMEDCENTRAL : PMC4238406

Éditeur(s) : HAL CCSD
Résumé : International audience
Kisspeptins are well known as mediators of the coordinated communication between the brain-pituitary axis and the gonads in many vertebrates. To test the hypothesis that gonadal steroids regulate kiss1 and kiss2 mRNA expression in European sea bass (a teleost fish), we examined the brains of gonad-intact (control) and castrated animals, as well as castrated males (GDX) and ovariectomized females (OVX) that received testosterone (T) and estradiol (E2) replacement, respectively, during recrudescence. In GDX males, low expression of kiss1 mRNA is observed by in situ hybridization in the caudal hypothalamus (CH) and the mediobasal hypothalamus (MBH), although hypothalamic changes in kiss1 mRNA levels were not statistically different among the groups, as revealed by real-Time PCR. However, T strongly decreased kiss2 expression levels in the hypothalamus, which was documented in the MBH and the nucleus of the lateral recess (NRLd) in GDX T-Treated sea bass males. Conversely, it appears that E2 evokes lowkiss1mRNAin the CH, while there were cells expressing kiss2 in the MBH and NRLd in these OVX females. These results demonstrate that kisspeptin neurons are presumably sensitive to the feedback actions of sex steroids in the sea bass, suggesting that the MBH represents a major site for sex steroid actions on kisspeptins in this species. Also, recent data provide evidence that both positive and negative actions occur in key factors involved in sea bass reproductive function, including changes in the expression of gnrh-1/gonadotropin, cyp19b, er and ar genes and sex steroid and gonadotropin plasma levels in this teleost fish. © 2016. Published by The Company of Biologists Ltd.
Journal of Experimental Biology

hal-01406072
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406072
DOI : 10.1242/jeb.137364
PUBMED : 27591305

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
UNLABELLED: Glioblastoma (GB) is the most frequent and aggressive tumor of the central nervous system. There is currently growing interest in proteomic studies of GB, particularly with the aim of identifying new prognostic or therapeutic response markers. However, comparisons between different proteomic analyses of GB have revealed few common differentiated proteins. The types of control samples used to identify such proteins may in part explain the different results obtained. We therefore tried to determine which control samples would be most suitable for GB proteomic studies. We used an isotope-coded protein labeling (ICPL) method followed by mass spectrometry to reveal and compare the protein patterns of two commonly used types of control sample: GB peritumoral brain zone samples (PBZ) from six patients and epilepsy surgery brain samples (EB) pooled from three patients. The data obtained were processed using AMEN software for network analysis. We identified 197 non-redundant proteins and 35 of them were differentially expressed. Among these 35 differentially expressed proteins, six were over-expressed in PBZ and 29 in EB, showing different proteomic patterns between the two samples. Surprisingly, EB appeared to display a tumoral-like expression pattern in comparison to PBZ. In our opinion, PBZ may be more appropriate control sample for GB proteomic analysis. BIOLOGICAL SIGNIFICANCE: This manuscript describes an original study in which we used an isotope-coded protein labeling method followed by mass spectrometry to identify and compare the protein patterns in two types of sample commonly used as control for glioblastoma (GB) proteomic analysis: peritumoral brain zone and brain samples obtained during surgery for epilepsy. The choice of control samples is critical for identifying new prognostic and/or diagnostic markers in GB.
ISSN: 1874-3919

inserm-00871494
http://www.hal.inserm.fr/inserm-00871494
http://www.hal.inserm.fr/inserm-00871494/document
http://www.hal.inserm.fr/inserm-00871494/file/ManuscritProt-accepted.pdf
DOI : 10.1016/j.jprot.2013.04.031

Éditeur(s) : HAL CCSD
Résumé : From the protolanguage born with Homo erectus, the modern human language of Homo sapiens has naturally diversified into tonal, stress-timed, or syllable-timed languages, although the definition of the syllable has yet to be established. Thus for a French speaker, the transition from a language punctuated by the syllable to a language punctuated by the lexical stress will be a delicate point in learning oral English. For this purpose, we recommend the implementation of a reprogramming of the articulatory gesture in the brains as evidenced by articulatory phonology. Through the arched beam, Broca's area of the French-speaking learner will inhibit the French-related data to send to Wernicke's area new information regarding the reception / production of oral English.
A partir du protolangage né avec Homo erectus, le langage humain moderne d'Homo sapiens s'est naturellement diversifié en langues tonales, accentuelles, ou syllabiques, bien que la définition de la syllabe reste encore à établir. Ainsi pour un francophone, le passage d'une langue rythmée par la syllabe à une langue rythmée par l'accent lexical sera un point délicat de l'apprentissage de l'anglais oral. Pour ce faire, nous préconisons la mise en place d'une reprogrammation de la gestuelle articulatoire telle qu'elle a pu être mise en évidence par la phonologie articulatoire. Par le biais du faisceau arqué, l'aire de Broca de l'apprenant francophone inhibera les données liées au français pour envoyer à l'aire de Wernicke de nouvelles informations quant à la réception / production de l'anglais oral. Mots clés : neurodidactique, anglais oral, phonologie articulatoire, aires du langage, mémoire procédurale et à long terme. Abstract: From the protolanguage born with Homo erectus, the modern human language of Homo sapiens has naturally diversified into tonal, stress-timed, or syllable-timed languages, although the definition of the syllable has yet to be established. Thus for a French speaker, the transition from a language punctuated by the syllable to a language punctuated by the lexical stress will be a delicate point in learning oral English. For this purpose, we recommend the implementation of a reprogramming of the articulatory gesture in the brains as evidenced by articulatory phonology. Through the arched beam, Broca's area of the French-speaking learner will inhibit the French-related data to send to Wernicke's area new information regarding the reception / production of oral English.
https://hal.archives-ouvertes.fr/hal-01626540

hal-01626540
https://hal.archives-ouvertes.fr/hal-01626540
https://hal.archives-ouvertes.fr/hal-01626540/document
https://hal.archives-ouvertes.fr/hal-01626540/file/Neurodidactique%20%20Comment%20le%20cerveau%20d%27un%20apprenant%20francophone%20peut-il%20se%20programmer%20sur%20une%20langue%20accentuelle..pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors (ERs), aromatase B (Aro-B) protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line (U251MG) transfected with different zebrafish ER subtypes (ERα, ERβ1 and ERβ2) was also used. Embryos were exposed either to estradiol (E2), Cd, E2+Cd or E2+Cd+Zn for 72 h and cells were exposed to the same treatments for 30 h. Our results show that E2 treatment promoted the transcriptional activation of ERs and increased Aro-B expression, at both the protein and mRNA levels. Although exposure to Cd, does not affect the studied parameters when administered alone, it significantly abolished the E2-stimulated transcriptional response of the reporter gene for the three ER subtypes in U251-MG cells, and clearly inhibited the E2 induction of Aro-B in radial glial cells of zebrafish embryos. These inhibitory effects were accompanied by a significant downregulation of the expression of esr1, esr2a, esr2b and cyp19a1b genes compared to the E2-treated group used as a positive control. Zn administration during simultaneous exposure to E2 and Cd strongly stimulated zebrafish ERs transactivation and increased Aro-B protein expression, whereas mRNA levels of the three ERs as well as the cyp19a1b remained unchanged in comparison with Cd-treated embryos. In conclusion, our results clearly demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced E2 antagonism can be reversed, at the protein level, by Zn supplement.
Journal of Applied Toxicology

Droits : info:eu-repo/semantics/OpenAccess
hal-01274217
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274217
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274217/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274217/file/Inhibitory%20effect%20of%20Cadmium%20on%20estrogen_accepted.pdf
DOI : 10.1002/jat.3285

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Neuroglobins, previously thought to be restricted to vertebrate neurons, were detected in the brain of a photosymbiotic acoel, Symsagittifera roscoffensis, and in neurosensory cells of the jellyfish Clytia hemisphaerica. For the neuroglobin of S. roscoffensis, a member of a lineage that originated either at the base of the bilateria or of the deuterostome clade, we report the ligand binding properties, crystal structure at 2.3 Å, and brain immunocytochemical pattern. We also describe in situ hybridizations of two neuroglobins specifically expressed in differentiating nematocytes (neurosensory cells) and in statocytes (ciliated mechanosensory cells) of C. hemisphaerica, a member of the early branching animal phylum cnidaria. In silico searches using these neuroglobins as queries revealed the presence of previously unidentified neuroglobin-like sequences in most metazoan lineages. Because neural systems are almost ubiquitous in metazoa, the constitutive expression of neuroglobin-like proteins strongly supports the notion of an intimate association of neuroglobins with the evolution of animal neural systems and hints at the preservation of a vitally important function. Neuroglobins were probably recruited in the first protoneurons in early metazoans from globin precursors. Neuroglobins were identified in choanoflagellates, sponges, and placozoans and were conserved during nervous system evolution. Because the origin of neuroglobins predates the other metazoan globins, it is likely that neuroglobin gene duplication followed by co-option and subfunctionalization led to the emergence of globin families in protostomes and deuterostomes (i.e. convergent evolution).
ISSN: 0021-9258

hal-01020584
http://hal.upmc.fr/hal-01020584
http://hal.upmc.fr/hal-01020584/document
http://hal.upmc.fr/hal-01020584/file/Rosko_jbc_revised.pdf
DOI : 10.1074/jbc.M112.407601

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In this study, we report the cloning of three transcripts for leptin receptor in the European sea bass, a marine teleost of economic interest. The two shortest variants, generated by different splice sites, encode all functional extracellular and intracellular domains but missed the transmembrane domain. The resulting proteins are therefore potential soluble binding proteins for leptin. The longest transcript (3605 bp), termed sblepr, includes all the essential domains for binding and transduction of the signal. Thus, it is proposed as the ortholog for the human LEPR gene, the main responsible for leptin signalling. Phylogenetic analysis shows the sblepr clustered within the teleost leptin receptor group in 100% of the bootstrap replicates. The neuroanatomical localization of sblepr expressing cells has been assessed by in situ hybridization in brains of sea bass of both sexes during their first sexual maturation. At histological level, the distribution pattern of sblepr expressing cells in the brain shows no clear differences regarding sex or reproductive season. Transcripts of the sblepr have a widespread distribution throughout the forebrain and midbrain until the caudal portion of the hypothalamus. A high hybridization signal is detected in the telencephalon, preoptic area, medial basal and caudal hypothalamus and in the pituitary gland. In a more caudal region, sblepr expressing cells are identified in the longitudinal torus. The expression pattern observed for sblepr suggests that in sea bass, leptin is very likely to be involved in the control of food intake, energy reserves and reproduction
ISSN: 0016-6480

hal-01290500
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01290500
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01290500/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01290500/file/Leptin%20receptor%20gene%20in%20the%20European%20sea%20bass%20postprint.pdf
DOI : 10.1016/j.ygcen.2016.03.017

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.
ISSN: 1932-6203

hal-01616489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616489
DOI : 10.1371/journal.pone.0184475
PUBMED : 29020013

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : Full text: http://jn.physiology.org/content/88/3/1475
International audience
The contribution of voltage-gated calcium channels (VGCC) to the development of cultured embryonic cockroach brain neurons was assessed using pharmacological agents. VGCC currents were recorded using the patch-clamp technique and were found to be blocked dose-dependently by micromolar concentrations of mibefradil. The activation and inactivation properties of the calcium channels enable a sizeable calcium current to flow at rest (about -30 and -20 mV in high-potassium culture media). As expected, the cytoplasmic-free calcium concentration was found to rise when the extracellular potassium concentration was raised from 3 to 15 and 30 mM. The effects of VGCC blockers and calcium chelators were different in fresh and in mature cultures in which the neurons were connected to each other to form a defined network. In fresh cultures, the two non-selective VGCC blockers (verapamil and mibefradil) induced a dose-dependent cell death that was proportional to their blocking effect on I(Ba). This effect could not be prevented by addition of fetal calf serum to the culture medium. A similar effect was obtained using intra- or extracellular calcium chelating agents (10 microM BAPTA-AM or 10 mM EGTA). Quite unexpectedly, blockade of the P/Q-like (omega-Aga WA-sensitive) component of the calcium current by 500 nM of omega-AgaTx IVA had no lethal effect, suggesting that the corresponding channels are not involved in the survival mechanism. As expected from their lack of effect on I(Ba), isradipine, nifedipine, and omega-CgTx GVIA did not induce cell death. When the neurons started growing neurites, their sensitivity to calcium channel blockade by mibefradil decreased, indicating a correlation between neurite outgrowth and resistance to calcium depletion. In mature cultures, the neurons became resistant to mibefradil, verapamil, and BAPTA-AM. However, these agents, as well as omega-AgaTx IVA, had a significant inhibitory effect on the increase in diameter of the connectives that linked adjacent clusters of neurons. This effect has been shown to result, in the case of mibefradil, from an inhibition of neurite outgrowth characterized by a significant reduction of the number of primary neurites and secondary branchings but not to a significant modification of the diameter of individual neurites. These results support the view that, as in vertebrates, calcium influx through VGCC plays an important role in survival and neurite outgrowth of cultured embryonic insect neurons. The differential contribution of the P/Q-like and R-like (omega-Aga WA-sensitive) calcium channels in these processes is discussed.
ISSN: 0022-3077

hal-00982287
https://hal.archives-ouvertes.fr/hal-00982287
DOI : 10.1152/jn.00749.2001
PUBMED : 12205168