Fiscal rule and shock amplification : A stochastic endogenous growth model

This paper develops a discrete-time stochastic endogenous growth model to study the amplification role of fiscal rules. In our model, transitory shocks exert permanent effects on the level of variables in equilibrium (hysteresis), and can be strongly amplified by the public debt adjustment, leading to a procyclical amplification mechanism (the "public debt accelerator"). This procyclical stance depends on the speed of adjustment of the debt-to-GDP ratio under a fixed-fiscal rule. A cold turkey strategy removes the public debt shock, but at the risk of destabilizing other variables, while a gradualist strategy has a stabilization effect, with detrimental consequences in the long-run. Finally, we show that a flexible-fiscal rule helps smooth aggregate variables by limiting the cuts in productive public spending

Vieillissement physiologique et pathologique du contrôle nerveux de la respiration (étude chez des souris sauvages et transgéniques)

De nouveaux enjeux émergent dans le domaine de la Santé en raison du vieillissement de la population et du développement inquiétant de la Maladie d Alzheimer (MA). Chez le sujet sain ou pathologique, peu d études ont porté sur le vieillissement du contrôle nerveux de la respiration, en dépit de son rôle crucial pour l oxygénation du cerveau. Cette thèse présente des recherches translationnelles, réalisées chez la souris, pour étudier le vieillissement physiologique et pathologique du contrôle nerveux de la respiration. Chez des souris transgéniques, modèles reconnus de la MA et du syndrome de Rett, nous décrivons le développement de neuropathologies respiratoires graves, conduisant à un décès prématuré. Nous montrons pour la première fois qu une tauopathie du tronc cérébral altère le fonctionnement des voies aériennes supérieures, la vocalisation et la respiration. De plus, nos travaux suggèrent un rôle délétère de l anesthésie pour la MA et identifient des pistes thérapeutiques nouvelles. En conclusion, nos travaux chez la souris peuvent avoir des retombées particulièrement intéressantes notamment pour la MA.New issues are emerging in the field of Health care due to ageing of the population and the alarming development of Alzheimer s Disease (AD). In healthy or pathological living being, very few studies are dealing with the ageing of the respiratory nervous control, in spite of the crucial role of respiration for brain oxygenation. This thesis presents translational research performed in mice to examine the physiological and pathological ageing of the respiratory nervous control. In mice from two transgenic strains, recognized models for AD and Rett syndrome, we describe the development of drastic respiratory neuropathologies leading to premature death. In the AD mouse model, we show for the first time that brainstem tauopathy triggers dysfunctions of the upper airways, impairs vocalization and alters respiration and respiratory control. In addition, our work suggests a deleterious effect of anaesthesia for AD and identifies new therapeutic strategies. This mouse research could well contribute to significant improvements in AD care.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Synthesis of estrogens in progenitor cells of adult fish brain: Evolutive novelty or exaggeration of a more general mechanism implicating estrogens in neurogenesis?

International audienceIn contrast to other vertebrates, in which the adult brain shows limited adult neurogenesis, teleost fishes exhibit an unparalleled capacity to generate new neurons as adults, suggesting that their brains present a highly permissive environment for the maintenance and proliferation of adult progenitors. Here, we examine the hypothesis that one of the factors permitting establishment of this favourable environment is estradiol. Indeed, recent data showed that radial glial cells strongly expressed one of two aromatase duplicated genes. Aromatase is the estrogen-synthesizing enzyme and this observation is of great interest, given that radial glial cells are progenitor cells capable of generating new neurons. Given the well-documented roles of estrogens on cell fate, and notably on cell proliferation, these data suggest that estradiol could be involved in maintaining and/or activating these progenitors. Examination of recent data in birds and mammals suggests that the situation in fish could well be an exaggeration of a more general mechanism implicating estrogens in neurogenesis. Indeed, there is accumulating evidence that estrogens are involved in embryonic, adult or reparative neurogenesis in other vertebrates, notably in mammals

Fluoxetine treatment abolishes the in vitro respiratory response to acidosis in neonatal mice

International audienceBACKGROUND: To secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response.METHODOLOGY/PRINCIPAL FINDINGS: Using en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25-50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice.CONCLUSIONS: These results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers

Time- and Dose-Related Effects of Di-(2-ethylhexyl) Phthalate and Its Main Metabolites on the Function of the Rat Fetal Testis in Vitro

International audienceBACKGROUND: Endocrine-disrupting effects of phthalates are understood primarily from in utero exposures within the fetal rat testis. Nevertheless, their path of action, dose-response character, and cellular target(s) within the fetal testis are not known. OBJECTIVES: In this study we investigated the effects of di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP), and several of their metabolites on the development of organo-cultured testes from rat fetus. METHODS: We removed testes from 14.5-day-old rat fetuses and cultured them for 1-3 days with or without DEHP, MEHP, and the metabolites. RESULTS: DEHP (10(-5) M) produced a proandrogenic effect after 3 days of culture, whereas MEHP disrupted testis morphology and function. Leydig cells were the first affected by MEHP, with a number of them being inappropriately located within some seminiferous tubules. Additionally, we found a time- and dose-dependent reduction of testosterone. By 48 hr, gonocyte proliferation had decreased, whereas apoptosis increased. Sertoli cell number was unaffected, although some cells appeared vacuolated, and production of anti-Müllerian hormone decreased in a time- and dose-dependent manner. The derived metabolite mono-(2-ethyl-5-hydroxyhexyl) phthalate was the only one to cause deleterious effects to the rat fetal testis in vitro. CONCLUSION: We hope that this in vitro method will facilitate the study of different phthalate esters and other endocrine disruptors for direct testicular effects

Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc

International audienceThe 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

Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula

The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification αacetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.This work was supported by grants from the Spanish Dirección General de Investigación-FEDER (BFU2010- 15816), the Xunta de Galicia (10PXIB200051PR, CN 2012/237), European Community-Research Infrastructure Action under the FP7 “Capacities” Specific Programme (ASSEMBLE 227799), the Région Centre, Région Bretagne (EVOVERT grant number 049755; PEPTISAN project), National Research Agency (grant ANR-09-BLAN-026201), CNRS, Université d’Orléans and Université Pierre et Marie Curie. GNSD would like to thank Spanish SEPE for its funding supportS

Developmental toxicity and brain aromatase induction by high genistein concentrations in zebrafish embryos

Genistein is a phytoestrogen found at a high level in soybeans. In vitro and in vivo studies showed that high concentrations of genistein caused toxic effects. This study was designed to test the feasibility of zebrafish embryos for evaluating developmental toxicity and estrogenic potential of high genistein concentrations. The zebrafish embryos at 24 h post-fertilization were exposed to genistein (1 × 10−4 M, 0.5 × 10−4 M, 0.25 × 10−4 M) or vehicle (ethanol, 0.1%) for 60 h. Genistein-treated embryos showed decreased heart rates, retarded hatching times, decreased body length, and increased mortality in a dose-dependent manner. After 0.25 × 10−4 M genistein treatment, malformations of survived embryos such as pericardial edema, yolk sac edema, and spinal kyphosis were also observed. TUNEL assay results showed apoptotic DNA fragments in brain. This study also confirmed the estrogenic potential of genistein by EGFP expression in the brain of the mosaic reporter zebrafish embryos. This study first demonstrated that high concentrations of genistein caused a teratogenic effect on zebrafish embryos and confirmed the estrogenic potential of genistein in mosaic reporter zebrafish embryos