Central Role of Glucocorticoid Receptors in Alzheimer’s Disease and Depression

Alzheimer’s disease (AD) is the principal neurodegenerative pathology in the world displaying negative impacts on both the health and social ability of patients and inducing considerable economic costs. In the case of sporadic forms of AD (more than 95% of patients), even if mechanisms are unknown, some risk factors were identified. The principal risk is aging, but there is growing evidence that lifetime events like chronic stress or stress-related disorders may increase the probability to develop AD. This mini-review reinforces the rationale to consider major depressive disorder (MDD) as an important risk factor to develop AD and points the central role played by the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids (GC) and their receptors (GR) in the etiology of MDD and AD. Several strategies directly targeting GR were tested to neutralize the HPA axis dysregulation and GC overproduction. Given the ubiquitous expression of GR, antagonists have many undesired side effects, limiting their therapeutic potential. However, a new class of molecules was developed, highly selective and acting as modulators. They present the advantage to selectively abrogate pathogenic GR-dependent processes, while retaining beneficial aspects of GR signaling. In fact, these “selective GR modulators” induce a receptor conformation that allows activation of only a subset of downstream signaling pathways, explaining their capacity to combine agonistic and antagonistic properties. Thus, targeting GR with selective modulators, alone or in association with current strategies, becomes particularly attractive and relevant to develop novel preventive and/or therapeutic strategies to tackle disorders associated with a dysregulation of the HPA axis

Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

Vitamin E, the most important lipophilic radical scavenging antioxidant in vivo, has a pivotal role in brain. In an earlier study, we observed that adult mice with a defect in the gene encoding plasma phospholipid transfer protein (PLTP) display a moderate reduction in cerebral vitamin E levels, and exacerbated anxiety despite normal locomotion and memory functions. Here we sought to determine whether dietary vitamin E supplementation can modulate neurotransmitter levels and alleviate the increased anxiety phenotype of PLTP-deficient (PLTP−/−) mice. To address this question, a vitamin E-enriched diet was used, and two complementary approches were implemented: (i) “early supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice born from vitamin E-supplemented parents; and (ii) “late supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice fed a vitamin E-enriched diet from weaning. Our results show for the first time that an inadequate supply of vitamin E during development, due to moderate maternal vitamin E deficiency, is associated with reduced brain vitamin E levels at birth and irreversible alterations in brain glutamate levels. They also suggest this deficiency is associated with increased anxiety at adulthood. Thus, the present study leads to conclude on the importance of the micronutrient vitamin E during pregnancy

Association of circulating metabolites with healthy diet and risk of cardiovascular disease : analysis of two cohort studies

Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations-the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 +/- 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 +/- 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.Peer reviewe

Validation de trois épreuves de raisonnement verbal, numérique et diagrammatique

International audienc

How do cyber- and traditional workplace bullying, organizational justice and social support, affect psychological distress among civil servants

This study examines the effects of cyber- and traditional workplace bullying,organizational justice, and social support on psychological distress.Using a cross-sectional design, we submitted an on-line questionnaire to 179French civil servants. Based on Hayes and Preacher’s (2014) method, theresults indicated that organizational justice as a whole and, specifically,interpersonal justice, were a partial mediator in the relationship betweentraditional bullying and psychological distress. Supervisor support was apartial mediator in the relationship between traditional bullying and psychologicaldistress, and, a complete mediator within the relationship between cyberbullyingand psychological stress. The inclusion of organizational justice asa mediator provided an interesting route, suggesting that it is essential to prevent the harmful consequences of bullying. Communication, respectful relationships,and above all support from supervisors are essential solutions fordecreasing psychological distress at work.info:eu-repo/semantics/publishe

Plasma phospholipid transfer protein (PLTP): review of an emerging cardiometabolic risk factor

International audiencePlasma phospholipid transfer protein (PLTP) is a lipid transfer glycoprotein that binds to and transfers a number of amphipathic compounds. In earlier studies, the attention of the scientific community focused on the positive role of PLTP in high-density lipoprotein (HDL) metabolism. However, this potentially antiatherogenic role of PLTP has been challenged recently by another picture: PLTP arose as a pro-atherogenic factor through its ability to increase the production of apolipoprotein B-containing lipoproteins, to decrease their antioxidative protection and to trigger inflammation. In humans, PLTP has mostly been studied in patients with cardiometabolic disorders. Both PLTP and related cholesteryl ester transfer protein (CETP) are secreted proteins, and adipose tissue is an important contributor to the systemic pools of these two proteins. Coincidently, high levels of PLTP and CETP have been found in the plasma of obese patients. PLTP activity and mass have been reported to be abnormally elevated in type 2 diabetes mellitus (T2DM) and insulin-resistant states, and this elevation is frequently associated with hypertriglyceridemia and obesity. This review article presents the state of knowledge on the implication of PLTP in lipoprotein metabolism, on its atherogenic potential, and the complexity of its implication in obesity, insulin resistance and T2DM

How do cyber- and traditional workplace bullying, organizational justice and social support, affect psychological distress among civil servants?

International audienc

What Makes Happy Counselors? From Self-Esteem and Leader-Member Exchange to Well-Being at Work: The Mediating Role of Need Satisfaction

This study was aimed at examining the extent to which well-being at work is linked to self-esteem and psychosocial resources such as leader-member exchange (LMX). Drawing on self-determination theory, we looked at whether psychological needs (perceived autonomy, competence, and relatedness) act as specific mediators between self-esteem and well-being, and between LMX and well-being. 224 employment counselors (psychologists) from a French national employment office (Pôle emploi) answered a questionnaire. The data were analyzed using Hayes and Preacher's method for testing multiple mediations. The results showed that satisfaction of psychological needs for autonomy, competence and relatedness mediated the links between self-esteem and LMX as inductors, and well-being as a criterion. These findings confirm the relevance of self-esteem and LMX for counselors, and of the importance of need satisfaction that plays a critical role in matters of well-being.info:eu-repo/semantics/publishe

What Makes Happy Counselors? From Self-Esteem and Leader-Member Exchange to Well-Being at Work: The Mediating Role of Need Satisfaction

International audienceThis study was aimed at examining the extent to which well-being at work is linked to self-esteem and psychosocial resources such as leader-member exchange (LMX). Drawing on self-determination theory, we looked at whether psychological needs (perceived autonomy, competence, and relatedness) act as specific mediators between self-esteem and well-being, and between LMX and well-being. Two hundred and twenty four employment counselors (psychologists) from a French national employment office (Pôle emploi) answered a questionnaire. The data were analyzed using Hayes and Preacher's method for testing multiple mediations. The results showed that satisfaction of psychological needs for autonomy, competence and relatedness mediated the links between self-esteem and LMX as inductors, and well-being as a criterion. These findings confirm the relevance of self-esteem and LMX for counselors, and of the importance of need satisfaction that plays a critical role in matters of well-being