Regulation of 11 beta-hydroxysteroid dehydrogenase in rat brain and cloning of the gene promoter region

Adrenal corticosteroid hormones play diverse and important roles in development and homeostasis. Their complex effects are predominantly mediated by intracellular receptors, which are of two types; mineralocorticoid (MR, type I) and glucocorticoid (GR, type II). MR bind aldosterone and physiological glucocorticoids (Cortisol, corticosterone) with equivalent high affinity in vitro, whereas GR show a low affinity for aldosterone but bind physiological glucocorticoids and the synthetic glucocorticoid dexamethasone with high affinity. In vivo, kidney MR selectively bind aldosterone despite a hundred-fold molar excess of circulating glucocorticoids. This selectivity is due to the high activity of the enzyme 11ß-hydroxysteroid dehydrogenase (11ß-OHSD) which catalyses the reversible conversion of physiological glucocorticoids to inactive products, but does not metabolise aldosterone, thus preventing glucocorticoid access to renal MR. This thesis describes firstly the presence and subregional distribution of 11ß-OHSD in rat brain using Northern analysis, in situ hybridisation, and an 11ß-OHSD activity assay. The enzyme was not only found in aldosterone selective regions, such as periventricular areas of the hypothalamus, but also in hippocampus where corticosterone is the physiological ligand for MR, and, more surprisingly, in cerebellum which contains very low levels of MR. Therefore it was postulated that 11ß-OHSD might modulate glucocorticoid access to both types of corticosteroid receptor in brain. Furthermore, brain but not renal, 11ß-OHSD was up-regulated by chronic glucocorticoid but not aldosterone administration, suggesting a role for the enzyme in controlling long-term neuronal glucocorticoid exposure. The importance of 11ß-OHSD in brain was further substantiated by the finding of high 11ß-OHSD mRNA levels and activity in rat brain subregions in the early postnatal period, with regionally specific developmental patterns of activity. The enzyme may play an important role in the developing brain by protecting tissues from (or exposing them to) elevated corticosterone levels. To understand the molecular mechanisms underlying tissuespecific and ontogenic regulation of 11ß-OHSD a rat genomic clone was isolated and partially sequenced. Differential promoter usage of the gene was demonstrated in kidney; three transcription start sites were detected within one kilobase of 5' flanking region of the gene, using primer extension and ribonuclease protection analyses. Corresponding transcripts were detected on Northern blots of kidney, but not liver RNA, using specific oligonucleotide probes. Sequence analysis revealed a number of putative transcription factor binding sites. These findings might explain, at least in part, tissue-specific differences in the regulation of 11ß-OHSD mRNA and activity

Sexual dimorphism in glucocorticoid stress response

Chronic stress is encountered in our everyday life and is thought to contribute to a number of diseases. Many of these stress-related disorders display a sex bias. Because glucocorticoid hormones are the main biological mediator of chronic stress, researchers have been interested in understanding the sexual dimorphism in glucocorticoid stress response to better explain the sex bias in stress-related diseases. Although not yet demonstrated for glucocorticoid regulation, sex chromosomes do influence sex-specific biology as soon as conception. Then a transient rise in testosterone start to shape the male brain during the prenatal period differently to the female brain. These organizational effects are completed just before puberty. The cerebral regions implicated in glucocorticoid regulation at rest and after stress are thereby impacted in a sex-specific manner. After puberty, the high levels of all gonadal hormones will interact with glucocorticoid hormones in specific crosstalk through their respective nuclear receptors. In addition, stress occurring early in life, in particular during the prenatal period and in adolescence will prime in the long-term glucocorticoid stress response through epigenetic mechanisms, again in a sex-specific manner. Altogether, various molecular mechanisms explain sex-specific glucocorticoid stress responses that do not exclude important gender effects in humans

Metabolism Open

Both diabetes types, types 1 and 2, are associated with cognitive impairments. Each period of life is concerned, and this is an increasing public health problem. Animal models have been developed to investigate the biological actors involved in such impairments. Many levels of the brain function (structure, volume, neurogenesis, neurotransmission, behavior) are involved. In this review, we detailed the part potentially played by the Hypothalamic-Pituitary Adrenal axis in these dysfunctions. Notably, regulating glucocorticoid levels, their receptors and their bioavailability appear to be relevant for future research studies, and treatment development

Le mal-être active les gènes codant pour l'inflammation

Les chevaux agressifs ne sont pas simplement des chevaux mal éduqués ou caractériels. Cette agressivité peut révéler des souffrances physiques et un état de mal-être qui peuvent être profonds. Cet état de mal-être va jusqu’à modifier l’expression de certains de leurs gènes : ceux impliqués dans la réponse immunitaire et au stress, et la mort cellulaire programmée. Cela montre à quel point ce trouble ne doit pas être pris à la légère. Les chevaux qui présentent un trouble agressif doivent être pris en charge afin de faire évoluer leurs conditions de vie et de travail vers une meilleure prise en compte de leur bien-être

Instruments de manutention des malades, usage du corps et appropriation des gestes collectifs des soignants

L’objectif de cet article est double : comprendre les effets de l’utilisation d’instruments d’aide à la manutention sur les contraintes d’exposition au risque de lombalgie et faire des recommandations aux professionnels de santé sur la façon de faire évoluer leur rapport aux instruments, ainsi que sur les critères et modalités d’utilisation sur lesquelles pourront s’appuyer les concepteurs. Les raisons motivant cette orientation de l’étude sont les suivants : constat d’une faible utilisation du matériel d’aides à la manutention dans les services de soins, des accidents lombalgiques très élevés lors de la manutention de patient, des préoccupations des décideurs des CHU centrés sur l’achat d’équipement.La méthodologie choisie repose sur un diagnostic ergonomique des activités de manutention de patients, à partir d’observations accompagnées de mesures comparant trois outils d’aide à la manutention de patient (alèse, matériel mobile, rail au plafond), de données issues d’expérimentation de nouveau matériel, et de données épidémiologiques sur les relations entre contraintes de manutention et effet sur la santé.The aim of this article is twofold: 1) to understand the consequences of using patient handling tools on the risk factors for Upper Extremity Musculoskeletal Disorders (UEMSDs) and low back pain; and 2) to make recommendations to health professionals about how to improve their relationship with the tools as well as about the utilization criteria and methods on which designers can base their work. The reasons for studying this aspect was the low use of patient handling tools in real practice, the high number of low back injuries during patient handling, and the concerns of UHC management about the purchase of equipment. The chosen methodology was based on an ergonomic diagnosis of patient handling activities, from observations accompanied by measurements comparing three patient handling tools (quilted pads, mobile equipment, rail on the ceiling), data resulting from testing new material, and epidemiological data on the relationships between handling constraints and health impacts.El objetivo de este artículo es doble : comprender los efectos de la utilización de instrumentos de ayuda a la manipulación de pacientes sobre los riesgos de exposición al riesgo de lumbalgias y hacer recomendaciones a los profesionales de la salud sobre la manera de hacer evolucionar su relación con tales instrumentos así como sobre los criterios y modalidades que puedan apoyar los conceptores de tales instrumentos. Las razones que motivan esta orientación del estudio son las siguientes : se constata la poca utilización del material de ayuda a la manipulación de pacientes en las unidades hospitalarias ; existe un número elevado de accidentes que producen lumbalgias durante esta manipulación ; los decididores de los centros hospitalarios universitarios (CHU) están centrados en la compra de este material. La metodología seleccionada reposa sobre : un diagnóstico ergonómico de las actividades de manipulación de pacientes a partir de observaciones con tres instrumentos de ayuda (sábana, material móvil, riel en el techo) ; el análisis de datos recogidos durante la experimentación de nuevos instrumentos, el análisis de datos epidemiológicos sobre las relaciones entre las dificultades de manipulación y su efecto sobre la salud del personal

Epigenetic modifications linked to memory impairments induced by a high-fat diet during adolescence

We have previously reported that an unrestricted high fat diet consumed during the adolescence period has been causally linked with hippocampal memory impairments in adulthood. Causal mechanisms reported include, prolonged stress induced inflammatory response, neuronal hyperexcitability and cerebral plasticity disruption in hippocampus. In this study we have looked at hippocampal gene expression and protein levels in mice fed normal chow (NC) or high fat (HF) diet for 12 weeks since weaning and sacrificed 30 min after the training phase of contextual fear conditioning (CFC), a classical hippocampus-dependent memory test, and compared them to home cage controls. We found that many immediate early genes were induced by CFC in both NC and HF groups compared to controls. Interestingly, 2-way ANOVA diet by CFC interaction was found for genes encoding for epigenetic modifiers such as histone deacetylase (Hdac3) and DNA methylase (Dnmt3a) or histone methylase (Suv39h2). Finally, phosphorylated glucocorticoid receptor was upregulated and BDNF downregulated in CFC mice on HF diet. These data are interesting in view of similar modifications observed in hippocampus in age-related memory impairments

Spontaneous intake of essential oils after a negative postnatal experience has long-term effects on blood transcriptome in chickens

Chicks subjected to early stressful factors could develop long-lasting effects on their performances, welfare and health. Free access to essential oils (EO) in poultry farming could mitigate these effects and potentially reduce use of antimicrobial drugs. This study on chicken analyzed long-lasting effects of post-hatch adverse conditions (Delayed group), and the impact of EO intake on blood physiological parameters and transcriptome. Half of the Control and Delayed groups had free access to EO, while the other half had only water for the first 13 days post-hatching. Blood analyses of metabolites, inflammation and oxidative stress biomarkers, and mRNA expression showed sex differences. Long-lasting effects of postnatal experience and EO intake persisted in blood transcriptome at D34. The early adverse conditions modified 68 genes in males and 83 genes in females. In Delayed males six transcription factors were over-represented (NFE2L2, MEF2A, FOXI1, Foxd3, Sox2 and TEAD1). In females only one factor was over-represented (PLAG1) and four under-represented (NFIL3, Foxd3, ESR2 and TAL

Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes

We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.info:eu-repo/semantics/publishedVersio