Effect of the social environment on olfaction and social skills in WT and mouse model of autism

Autism spectrum disorders are complex, polygenic and heterogenous neurodevelopmental conditions, imposing a substantial economic burden. Genetics are influenced by the environment, specifically the social experience during the critical neurodevelopmental period. Despite efficacy of early behavior interventions targeted specific behaviors in some autistic children, there is no sustainable treatment for the two core symptoms: deficits in social interaction and communication, and stereotyped or restrained behaviors or interests. In this study, we investigated the impact of the social environment on both wild-type (WT) and Shank3 knockout (KO) mice, a mouse model that reproduces core autism-like symptoms. Our findings revealed that WT mice raised in an enriched social environment maintained social interest towards new conspecifics across multiple trials. Additionally, we observed that 2 hours or chronic social isolation induced social deficits or enhanced social interaction and olfactory neuron responses in WT animals, respectively. Notably, chronic social isolation restored both social novelty and olfactory deficits, and normalized self-grooming behavior in Shank3 KO mice. These results novel insights for the implementation of behavioral intervention and inclusive classrooms programs for children with ASD

Psycho-education programme for temporomandibular disorders: a pilot study

BACKGROUND: Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care. The aim of this pilot study was to develop a simple, cost-effective management programme for TMDs using CD-ROM. 41 patients (age 18–70) participated in this study, patients were divided into three groups: the 1st group were involved in an attention placebo CD-ROM (contain anatomical information about the temporomandibular system), the 2nd group received information on CD-ROM designed to increase their control and self efficacy, while the 3rd group received the same programme of the 2nd group added to it an introduction to self-relaxing techniques followed by audio tape of progressive muscle relaxation exercises. Each of the groups was asked to complete a number of questionnaires on the day of initial consultation and six weeks afterwards. RESULTS: The two experimental groups (2nd & 3rd) were equally effective in reducing pain, disability and distress, and both were more effective than the attention placebo group (1st), however the experimental groups appeared to have improved at follow-up relative to the placebo-group in terms of disability, pain and depressed mood. CONCLUSION: This pilot study demonstrates the feasibility and acceptability of the design. A full, randomized, controlled trial is required to confirm the efficacy of the interventions developed here

Hepatocyte endocannabinoid system and innate immunity influence whole-body lipid metabolism : investigation of the molecular mechanisms in the context of obesity

Nowadays, the prevalence of obesity-related liver diseases is increasing around the globe. However, the efficacy of the available treatments is still limited suggesting that new therapeutic strategies must be discovered. In this thesis we aimed to understand better the etiology of hepatic disorders by examining the impact of two proteins: the first one belonging to the immune system (MyD88) and the second one to the endocannabinoid system (NAPE-PLD). To reach this goal, we investigated the consequence of their deletion in hepatocytes in two distinct mouse models (Myd88∆Hep and Napepld∆Hep). Surprisingly, we discovered that both mutant mice were prone to liver inflammation and hepatic fat accumulation. Additionally, one crucial bioactive lipid family (i.e. bile acids) that regulates host homeostasis and inflammation was strongly altered in both Myd88∆Hep and Napepld∆Hep mice compared to WT. This thesis thereby provides new insights into the regulation of bile acids by two systems that seemed, at first, unrelated to this lipid family and emphasizes the importance of a proper regulation of molecules involved in their regulation to tackle the emergence of metabolic disorders.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202

LA MIGRAINE ET SON TRAITEMENT

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

The Liver under the Spotlight: Bile Acids and Oxysterols as Pivotal Actors Controlling Metabolism

Among the myriad of molecules produced by the liver, both bile acids and their precursors, the oxysterols are becoming pivotal bioactive lipids which have been underestimated for a long time. Their actions are ranging from regulation of energy homeostasis (i.e., glucose and lipid metabolism) to inflammation and immunity, thereby opening the avenue to new treatments to tackle metabolic disorders associated with obesity (e.g., type 2 diabetes and hepatic steatosis) and inflammatory diseases. Here, we review the biosynthesis of these endocrine factors including their interconnection with the gut microbiota and their impact on host homeostasis as well as their attractive potential for the development of therapeutic strategies for metabolic disorders

Etude du montage et du pelliculage de microgranules en lit fluidisé (comparaison de films acryliques et cellulosiques à libération prolongée en milieu aqueux ; influence des plastifiants)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

A powerful long metabarcoding method for the determination of complex diets from faecal analysis of the European pond turtle ( Emys orbicularis , L. 1758)

High‐throughput sequencing has become an accurate method for the identification of species present in soil, water, faeces, gut or stomach contents. However, information at the species level is limited due to the choice of short barcodes and based on the idea that DNA is too degraded to allow longer sequences to be amplified. We have therefore developed a long DNA metabarcoding method based on the sequencing of short reads followed by de novo assembly, which can precisely identify the taxonomic groups of organisms associated with complex diets, such as omnivorous individuals. The procedure includes 11 different primer pairs targeting the COI gene, the large subunit of the ribulose‐1,5‐bisphosphate carboxylase gene, the maturase K gene, the 28S rRNA and the trnL‐trnF chloroplastic region. We validated this approach using 32 faeces samples from an omnivorous reptile, the European pond turtle (Emys orbicularis, L. 1758). This metabarcoding approach was assessed using controlled experiments including mock communities and faecal samples from captive feeding trials. The method allowed us to accurately identify prey DNA present in the diet of the European pond turtles to the species level in most of the cases (82.4%), based on the amplicon lengths of multiple markers (168–1,379 bp, average 546 bp), and produced by de novo assembly. The proposed approach can be adapted to analyse various diets, in numerous conservation and ecological applications. It is consequently appropriate for detecting fine dietary variations among individuals, populations and species as well as for the identification of rare food items

PPZ 6: "Welcome" Worktape

Eight tracks (migrated from ADAT to an 8-track WAV file) recorded by Team Fat on ADAT tape for the song "Welcome," featured in the game "Putt-Putt Saves the Zoo."Dolph Briscoe Center for American Histor

Hepatic MyD88 regulates liver inflammation by altering synthesis of oxysterols.

This study aimed to investigate the function of hepatic myeloid differentiation primary response gene 88 (MyD88), a central adaptor of innate immunity, in metabolism. Although its role in inflammation is well known, we have recently discovered that MyD88 can also mediate energy, lipid, and glucose metabolism. More precisely, we have reported that mice harboring hepatocyte-specific deletion of (Myd88) were predisposed to glucose intolerance, liver fat accumulation, and inflammation. However, the molecular events explaining the onset of hepatic disorders and inflammation remain to be elucidated. To investigate the molecular mechanism, Myd88 and wild-type (WT) mice were challenged by two complementary approaches affecting liver lipid metabolism and immunity. The first approach consisted of a short-term exposure to high-fat diet (HFD), whereas the second was an acute LPS injection. We discovered that upon 3 days of HFD Myd88 mice displayed an increase in liver weight and liver lipids compared with WT mice. Moreover, we found that bile acid and oxysterol metabolism were deeply affected by the absence of hepatic MyD88. Our data suggest that the negative feedback loop suppressing bile acid synthesis was impaired (i.e., ERK activity was decreased) in Myd88 mice. Finally, the predisposition to inflammation sensitivity displayed by Myd88 mice may be caused by the accumulation of 25-hydroxycholesterol, an oxysterol linked to inflammatory response and metabolic disorders. This study highlights the importance of MyD88 on both liver fat accumulation and cholesterol-derived bioactive lipid synthesis. These are two key features associated with metabolic syndrome. Therefore, investigating the regulation of hepatic MyD88 could lead to discovery of new therapeutic targets

Microbial regulation of organismal energy homeostasis

The gut microbiome has emerged as a key regulator of host metabolism. Here we review the various mechanisms through which the gut microbiome influences the energy metabolism of its host, highlighting the complex interactions between gut microbes, their metabolites and host cells. Among the most important bacterial metabolites are short-chain fatty acids, which serve as a direct energy source for host cells, stimulate the production of gut hormones and act in the brain to regulate food intake. Other microbial metabolites affect systemic energy expenditure by influencing thermogenesis and adipose tissue browning. Both direct and indirect mechanisms of action are known for specific metabolites, such as bile acids, branched chain amino acids, indole propionic acid and endocannabinoids. We also discuss the roles of specific bacteria in the production of specific metabolites and explore how external factors, such as antibiotics and exercise, affect the microbiome and thereby energy homeostasis. Collectively, we present a large body of evidence supporting the concept that gut microbiota-based therapies can be used to modulate host metabolism, and we expect to see such approaches moving from bench to bedside in the near future