Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
INTRODUCTION:The frequency, the clinical characteristics, and the prognosis of dengue is highly variable. Dengue fever is associated with a range of neurological manifestations. The objective of the present study was to determine the incidence of neurological signs and their predictive factors using data from cases of dengue seen and followed in Cayenne Hospital during the Dengue 2 epidemic in 2013.METHODS:In 2013, a longitudinal study using data from all cases of dengue seen in Cayenne hospital was collected. Medical records used a standardized form to collect demographic information, clinical signs and biological results and the date at which they were present. The analysis used Cox proportional modeling to obtain adjusted Hazard ratios.RESULTS:A total of 1574 patients were included 221 of whom developed central nervous system signs. These signs were spontaneously resolutive. There were 9298person days of follow-up and the overall incidence rate for central nervous system signs was 2.37 per 100 person-days. The variables independently associated with central nervous system anomalies were headache, Adjusted Hazard ratio (AHR) = 1.9(95%CI = 1.4-2.6), bleeding AHR = 2 ((95%CI = 1.3-3.1), P = 0.001, abdominal pain AHR = 1.9 ((95%CI = 1.4-2.6), P<0.001, aches AHR = 2.1 ((95%CI = 1.5-2.9), P<0.001, and fatigue AHR = 1.5 ((95%CI = 1.3-1.7), P<0.001.DISCUSSION:Overall, the present study suggests that neurological signs of dengue are not exceptional even in patients without the most severe features of dengue. These manifestations were spontaneously resolutive. Here it was not possible to distinguish between encephalitis or encephalopathy. Further studies would require more in depth exploration of the patients.
ISSN: 1932-6203

inserm-01421218
http://www.hal.inserm.fr/inserm-01421218
http://www.hal.inserm.fr/inserm-01421218/document
http://www.hal.inserm.fr/inserm-01421218/file/2016%2C%20Djossou%20-%20Incidence%20and%20Predictive%20Factors%20of%20Central%20Nervous%20System%20Dysfunction%20in%20Patients%20Consulting.pdf
DOI : 10.1371/journal.pone.0150828.t003

Éditeur(s) : Imprimerie "La presse," Imprimerie "La presse," ( Port-au-Prince, Haïti )
Résumé : At head of title: ... Médico-sociologie.
Author's name at head of title: Dr. J.C. Dorsainvil.
Reprinted from Haïti médicale, 1913.

07219287
33018575
ocm07219287

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BackgroundRecent evidence suggests that autonomic nervous system activity could be involved in thepathophysiology of sickle cell disease, but it is unclear whether differences in autonomic nervoussystem activity are detectable during steady state in patients with mild and severe disease.The aim of the present study was to compare the autonomic nervous system activity, bloodrheology, and inflammation in patients with sickle cell anemia according to the frequency ofacute pain crisis.Design and MethodsTwenty-four healthy volunteers, 20 patients with sickle cell anemia with milder disease, and15 patients with sickle cell anemia with more severe disease were recruited. Milder disease wasdefined as having no pain crisis within the previous year. More severe disease was defined ashaving had within the previous year three or more pain crises which were documented by aphysician and required treatment with narcotics. The autonomic nervous system activity wasdetermined by spectral analysis of nocturnal heart rate variability. Blood viscosity determinationand measurements of several inflammatory markers (interleukin-6, soluble vascular celladhesion molecule-1, soluble CD40 ligand and sL-selectin) were made on blood samples collectedin steady-state conditions.ResultsResults showed that: 1) patients who had suffered more frequent pain crises had lowerparasympathetic activity and greater sympatho-vagal imbalance than both controls andpatients with milder disease. However, when adjusted for age, no significant difference wasdetected between the two sickle cell anemia patient groups; 2) patients who had suffered morefrequent pain crises had higher blood viscosity than patients with milder disease, and this wasnot dependent on age.ConclusionsResults from the present study indicate that both the autonomic nervous system activity andblood viscosity are impaired in patients with sickle cell anemia exhibiting high frequency ofpain crisis in comparison with those who did not experience a crisis within the previous year.
ISSN: 0390-6078

hal-01163973
https://hal.univ-antilles.fr/hal-01163973
DOI : 10.3324/haematol.2011.047365

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood-brain barrier. This review describes the basic structure and functions of this blood-nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood-nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.
ISSN: 0265-0215

hal-01477207
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477207
DOI : 10.1097/EJA.0000000000000590
PUBMED : 28146457

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
Résumé : Due to their phylogenetic position outside from Bilateria, cnidarians and ctenophores are key phyla to understanding the origin and early evolution of molecular mechanisms, cell types, or body plan features at the level of Metazoa. Unlike other non-bilaterian phyla (sponges and placozoans), they possess neurons and muscle cells. The first part of my work relates to the problem of the origin of the metazoan nervous system. Recent studies have suggested a dual origin for nerve cells, with ctenophore neurons having emerged independently from those of cnidarians and bilaterians. This hypothesis relies on phylogenomic analyses supporting ctenophores as sister-group to all other metazoans, and on the purported absence in ctenophores of almost all well-known neuro-transmission systems, including the cholinergic system. Refuting this claim, I present substantial evidence in favour of acetylcholine (Ach) being used in the ctenophore Pleurobrachia pileus as an extra-cellular messenger, including within the nervous system. This conclusion arises from the conjunction of multiple approaches at the molecular scale (orthology analyses, Ach immuno-localisation, gene in situ hybridisation), at the cellular scale (calcium imaging on muscle cells exposed to Ach) and at the organism scale (pharmacological treatments with an Ach analogue and Ach antagonists). In the second part of my thesis, I address the conservation of molecular mechanisms involved in the control of cellular proliferation. Notably, the Hippo pathway is known for its role in bilaterians in the negative control of cellular proliferation. I show that components of this pathway are conserved in Pleurobrachia pileus and in Clytia hemisphaerica and that the nuclear vs. cytoplasmic localisation of the transcriptional co-factor Yorkie is correlated to the extent of proliferation within C. hemisphaerica tissues. Finally, RNAseq differential gene expression analyses along a cellular conveyor belt of the C. hemisphaerica medusa suggests a tendency for conservation of function among a set of genes whose mammalian orthologues have documented roles in the arrest of cellular proliferation.
Les Cnidaires et les Cténaires sont deux embranchements extérieurs aux Bilatériens qui, de par leur position phylogénétique, constituent des modèles d'étude cruciaux pour comprendre l'origine et l'évolution de mécanismes moléculaires ou encore de types cellulaires à grande échelle chez les Métazoaires. Ils sont les deux seuls embranchements non-Bilatériens à posséder des cellules nerveuses ainsi que des cellules musculaires. La première partie de mon travail de thèse s'inscrit dans le contexte de la compréhension de l'origine du système nerveux des Métazoaires. Des études récentes suggèrent une origine double du système nerveux ; ainsi celui des Cténaires aurait été acquis de manière convergente par rapport à celui des Cnidaires et des Bilatériens. Cela repose sur des données récentes de phylogénomique proposant les Cténaires en tant que groupe-frère de tous les autres Métazoaires et sur l'absence supposée chez les Cténaires de quasiment tous les systèmes de neurotransmission connus y compris le système cholinergique. A l'encontre de ces hypothèses, j'ai pu mettre en évidence l'existence d'un système cholinergique chez le Cténaire Pleurobrachia pileus ainsi que son étroite association avec le système nerveux. Cette conclusion repose sur une multiplicité d'approches à l'échelle moléculaire (analyses d'orthologie, immunolocalisation, hybridations in situ), cellulaire (imagerie calcique) et de l'organisme (approche pharmacologique). Dans la seconde partie de ma thèse, j'aborde la question de la conservation des mécanismes moléculaires impliqués dans le contrôle de la prolifération cellulaire à l'échelle des Métazoaires. J'ai pu mettre en évidence la conservation des acteurs.
https://tel.archives-ouvertes.fr/tel-01633223

NNT : 2015PA066629
tel-01633223
https://tel.archives-ouvertes.fr/tel-01633223
https://tel.archives-ouvertes.fr/tel-01633223v2/document
https://tel.archives-ouvertes.fr/tel-01633223/file/2015PA066629.pdf

Éditeur(s) : HAL CCSD Masson
Résumé : National audience
Started in 2015 in Brazil, an outbreak linked to a little known arbovirus, Zika virus spread throughout Latin America. This virus, considered until recently as responsible of only mild symptoms, made mention of previously unsuspected complications, with severe neurological manifestations in adults and malformations of the central nervous system, including microcephaly, in newborns of mother infected during the pregnancy. While the continent is more accustomed to the succession of arbovirus epidemics, suspected complications and the many unknowns keys of the latter arriving raise many public health issues. French Guiana, a French territory located in the north-east of the continent, combines both European level of resources and climate and issues specific to the Amazon region and Latin America. We discuss here the issues for 2016 Zika virus epidemic in our region, many of them are generalizable to neighboring countries.
ISSN: 0037-9085

inserm-01422054
http://www.hal.inserm.fr/inserm-01422054
http://www.hal.inserm.fr/inserm-01422054/document
http://www.hal.inserm.fr/inserm-01422054/file/2016%2C%20Epelboin%20-%20%C3%89pid%C3%A9mie%20de%20virus%20Zika%20en%20Am%C3%A9rique%20latine%20-%20quels%20enjeux%20pour%20la%20Guyane%20%281%29.pdf
DOI : 10.1007/s13149-016-0490-5

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A decreased global autonomic nervous system (ANS) activity and increased sympathetic activation in patients with sickle cell anemia (SCA) seem to worsen the clinical severity and could play a role in the pathophysiology of the disease, notably by triggering vaso-occlusive crises. Because exercise challenges the ANS activity in the general population, we sought to determine whether a short (,15 min) and progressive moderate exercise session conducted until the first ventilatory threshold had an effect on the ANS activity of a group of SCA patients and a group of healthy individuals (CONT group). Temporal and spectral analyses of the nocturnal heart rate variability were performed before and on the 3 nights following the exercise session. Standard deviation of all normal RR intervals (SDNN), total power, low frequencies (LF) and high frequencies powers (HF) were lower but LF/HF was higher in SCA patients than in the CONT group. Moderate exercise did not modify ANS activity in both groups. In addition, no adverse clinical events occurred during the entire protocol. These results imply that this kind of short and moderate exercise is not detrimental for SCA patients.
ISSN: 1932-6203

hal-01136725
https://hal.univ-antilles.fr/hal-01136725
https://hal.univ-antilles.fr/hal-01136725/document
https://hal.univ-antilles.fr/hal-01136725/file/Hedreville%20et%20al.%20-%202014%20-%20Acute%20moderate%20exercise%20does%20not%20further%20alter%20the%20autonomic%20nervous%20system%20activity%20in%20patients%20with%20sick%282%29.pdf
DOI : 10.1371/journal.pone.0095563

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother’s genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architecture – and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model.
ISSN: 0018-506X

hal-01169791
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169791
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169791/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169791/file/Neuroplasticity%20In%20The%20Maternal%20Hippocampus_accepted.pdf
DOI : 10.1016/j.yhbeh.2015.06.004

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
ISSN: 1470-1626

hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/file/Prenatal%20exposures%20to%20paracetamol-accepted.pdf
DOI : 10.1530/REP-17-0165

Résumé : Les pathologies inflammatoires démyélinisantes primitives du système nerveux central (SNC) sont dominées par deux entités : la sclérose en plaques (SEP) et la neuromyélite optique (NMO). Ces deux pathologies se différencient par : 1. leur phénotype, la NMO se caractérisant par une myélite extensive dans le plan transversal et longitudinal et peu de lésions encéphaliques initiales ; 2. leur sévérité, le pronostic de la NMO étant moins bon que celui de la SEP ; 3. leur mécanisme immunologique, puisque l’immunité humorale domine nettement dans la NMO, cette pathologie répondant peu ou pas aux traitementshabituellement prescrits dans la SEP. Un anticorps sérique (IgG-NMO) a été retrouvé chez les patients atteints de NMO avec une sensibilité de 50-70% et une spécificité de 90-100%. Cet anticorps a pour cible le principal canal hydrique du SNC, l’aquaporine-4 (AQP4), qui se situe principalement sur les pieds astrocytaires jalonnant la barrière hémato-encéphalique. La SEP est relativement familière des neurologues car décrite sur le plan épidémiologique et dans son histoire naturelle depuis plus d’un siècle à travers de larges séries réalisées parfois en population générale. Son approche thérapeutique progresse suite à des essais contrôlés qui s’accumulent depuis maintenant près de 20 ans. Toutefois, la majorité des travaux ont été effectués chez les populations Caucasiennes en raison de sa plus grande fréquence dans ces populations. A l’inverse, la NMO garde encore un relatif mystère à cause de sa relative rareté, l’établissement très récent de critères diagnostiques et une physiopathologie très récemment éclaircie par la découverte de l’IgG-NMO qui a indiscutablement suscité un regain d’intérêt de cette affection. Ainsi, son incidence est quasiment inconnue de même que sa susceptibilité génétique. La progression du handicap de la NMO qu’il soit visuel ou moteur à l’évidence sévère, ne repose toujours pas sur des chiffres précis, la description des lésions neuroradiologiques reste encore très embryonnaire. Enfin, même s’il existe un consensus pour traiter énergiquement les poussées de NMO et les espacer, il n’existe quasiment aucune étude prospective.
Introduction: Aim of the study is to describe épidemiology, phenotype and treatment of demyelinating inflammatory diseases of the central nervous system (CNS) namely multiple sclerosis (MS) and neuromyelitis optica (NMO) in French West Indies.Epidemiology: MS emerged in the French West Indian (FWI) population with an incidence of 1.27/100 000 (CI 95%: 1.16-1.38) for the period 1992-2007 while incidence of NMO remained stable at 0.19/100,000 (CI 95%: 0.15–0.23). Both migration in Metropolitean France (MF) and decrease of sun exposure were risk factors for MS acquisition in FWI. Phenotype and treatment of NMO: NMO is a very rapidly disabling disease with median times to reach DSS 3, 6 and 8 of one year, 8 years and 22 years respectively. However, treatment by plasma exchanges were shown to reduce sequellae of NMO attacks ; mitoxantrone and rituximab reduced significantly annualized relapse rate (ARR) from 1.7 to 0.29 (p<10-4) and from 1,34 to 0,56 (p=0.0005) respectively, improving dramatically natural course of NMO.Phenotype and treatment of MS: Absence of Migration in MF in MS patients was found to be the strongest independent predictive factor of disability progression to DSS 6 (hazard ratio, 2.59; p=0.0002); beside short time to DSS3 (p=0.005), later age at onset (p=0.005), and multi-symptomatic onset (p=0.03). Treatment of MS by interferon beta-1 had a moderate impact in MS while natalizimab proved to be highly effective by reducing drastically ARR and inflammatory parameters on magnetic resonance imaging. Conclusion: Spectrum of demyelinating inflammatory disorders of CNS has reversed in French West Indies with overrepresentation of MS. Agressive therapy is needed to improve prognosis of NMO. Rapidly increasing of its incidence makes MS a new public health problem in French West Indies.

http://www.theses.fr/2012AGUY0511/document

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfER alpha, zfER beta 1 or zfER beta 2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.
ISSN: 0041-008X

hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/file/Several%20synthetic%20progestins%20disrupt%20the%20glial%20cell.pdf
DOI : 10.1016/j.taap.2016.05.019

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 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 Elsevier
Résumé : International audience
Dietary exposure to pesticide residues may present a risk to public health, especially for sensitive populations such as pregnant women. To characterize this risk, this study assessed chronic dietary exposure to pesticide residues based on the French ELFE cohort. A self-administered food frequency questionnaire (FFQ) about the last three months of pregnancy filled in by pregnant women in 2011 was used in combination with occurrence data from French Total Diet Studies completed by the results of national monitoring programs on pesticide residues in food. The dietary intake of pesticides (μg/kg of body weight/day) was estimated for 14,099 pregnant women with a complete FFQ, for 317 substances under two occurrence scenarios to handle left-censored data: a lower-bound scenario (LB), where undetected results were set to zero, and an upper-bound scenario (UB), where undetected results were set to the detection limit if the substance was expected to be found in food and zero if it was not. The risk was assessed for 284 substances with a toxicological reference value (TRV) and a good coverage level of the diet potentially contributing to pesticide intake. The cumulative risk was also assessed for seven effects on nervous and thyroid systems using the hazard index and the Cumulative Assessment Groups defined by EFSA. Substances with the highest exposure levels under the LB scenario were, in decreasing order, imazalil, piperonyl butoxide, chlorpropham, thiabendazole, iprodione and propargite. Under the LB scenario, only for lindane did women have a statistically significant probability of exceeding the TRV (2.4%). Under the UB scenario, risk could not be excluded for nine other substances. A better management of left-censored data and more sensitive analyses of the main food contributors might help to refine the UB exposure and risk assessments. A statistically significant cumulative risk was found for neurochemical effects related to high intake levels of three organophosphate insecticides (chlorpyrifos, pirimiphos-methyl and dimethoate) mainly detected in fruits and cereals
ISSN: 0160-4120

hal-01319892
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01319892
DOI : 10.1016/j.envint.2016.04.007
PUBMED : 27187793

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Glioblastoma (GB), the most frequent primary tumor of the central nervous system, remains one of the most lethal human cancers despite intensive researches. Current paradigm in the study of GB has been focused on inter-patient variability and on trying to isolate new classification elements or prognostic factors. Here, using ICPL, a technique for protein relative quantification by mass spectrometry, we investigated protein expression between the four regions of GB on clinically relevant biopsies from 5 patients. We identified 584 non-redundant proteins and 31 proteins were found to be up-regulated in the tumor region compared to the peri-tumoral brain tissue, among which, 24 proteins belong to an interaction network linked to 4 biological processes. The core of this network is mainly constituted of interactions between beta-actin (ACTB) with heat shock proteins (HSP90AA1, HSPA8) and 14-3-3 proteins (YWHAZ, YWHAG, YWHAB). A cluster of three isoforms of the sodium pump α-subunit (ATP1A1, ATP1A2, ATP1A3) was also identified outside this network. The differential expression observed for ACTB and 14-3-3γ was further validated by western blot and/or immunohistochemistry. Our study confirms the identity of previously proposed molecular targets, highlights several functional processes altered in GB such as energy metabolism and synaptic transmission and could thus provide added value to new therapeutic trails.
ISSN: 1874-3919

hal-00877756
https://hal.archives-ouvertes.fr/hal-00877756
DOI : 10.1016/j.jprot.2012.04.034
PUBMED : 22575386

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 Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To better select for patients who most likely will benefit from cardiac surgery among those with infective endocarditis (IE), we aimed to identify preoperative markers associated with poor outcome after cardiac surgery for IE, and to evaluate the accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II to predict mortality. METHODS: We enrolled all adult patients who underwent cardiac surgery during the acute phase of definite IE (Duke Criteria) in two referral centres for cardiac surgery. Patients were identified through intensive care unit (ICU) electronic databases, and data were collected from medical charts on standardized questionnaire. RESULTS: Between 2002 and 2013, 149 patients (117 males), with a median age of 64 years [interquartile range 52-73], fulfilled the inclusion criteria. Main complications before surgery were left ventricular dysfunction (23%), central nervous system symptomatic events (34%) and septic shock (24%). Most patients (95%) presented with valve regurgitation, and 49% had perivalvular abscess. Surgery was performed with a median delay of 12 days [5-24] after IE diagnosis, and mean EuroSCORE II was 15.8 (13.4-18.1). In-hospital mortality was 21%. Preoperative variables associated with mortality in multivariate analysis were obesity [odds ratio (OR) 3.67 [1.10-12.19], P = 0.03], vegetation extgreater15 mm (OR 6.72 [1.46-30.98], P = 0.01), septic shock (OR 4.87 [1.67-14.28], P = 0.004) and mechanical prosthetic valve IE (OR 4.99 [1.72-28.57], P = 0.007). EuroSCORE II underestimated mortality in patients with predicted mortality over 10%. CONCLUSION: Factors independently predictive of mortality after cardiac surgery for IE are obesity, septic shock, large vegetation and a mechanical prosthetic valve IE. EuroSCORE II underestimates post-cardiac surgery mortality in patients with IE
ISSN: 1010-7940

hal-01169802
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169802
DOI : 10.1093/ejcts/ezv223
PUBMED : 26116921

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: Many women who work during pregnancy are occupationally exposed to toxicants. The developing central nervous system is highly vulnerable to neurotoxicants such as solvents. Although the neurotoxicity of solvents to adults is well established, very few studies have examined their effects on children's behaviour following prenatal exposure. METHODS: Women from the Perturbateurs endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance (PELAGIE) mother-child cohort (including 3005 working women) were recruited in Brittany (France) between 2002 and 2006, at the beginning of pregnancy, to assess occupational exposure to solvents at that time. Child behaviour was documented at age 2 by mothers (n=1278) assessing components of attention deficit/hyperactivity, aggression, opposition and emotionality. We used a multiple linear regression analysis to evaluate the association between occupational solvent exposure and children's behaviour. Complementary sensitivity analyses allowed us to handle missing data, due mostly to attrition. RESULTS: 20% of women reported occasional exposure and 31% regular exposure to solvents. Children prenatally exposed were more likely to have higher scores of attention deficit/hyperactivity and aggression, and dose-response relations were observed. CONCLUSIONS: The dose-response effect and the high prevalence of children potentially exposed to solvents from their mother's workplace exposure underline the public health relevance of this result. Our results should be replicated in further studies designed to identify which solvents are most deleterious and to assess child behaviour at school age.
ISSN: 1351-0711

inserm-00795043
http://www.hal.inserm.fr/inserm-00795043
http://www.hal.inserm.fr/inserm-00795043/document
http://www.hal.inserm.fr/inserm-00795043/file/Occupationnal_solvent_exposure_child_behavior_HAL.pdf
DOI : 10.1136/oemed-2012-100892

Éditeur(s) : HAL CCSD
Résumé : International audience
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. © 2016 Wiley Periodicals, Inc.
Journal of Comparative Neurology

hal-01439354
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01439354
DOI : 10.1002/cne.24077
PUBMED : 27414756