Maternal high-fat diet prevents developmental programming by early-life stress

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.Environnement psychosocial précoce, empreintes biologiques et épigénétiques et état de santé à l'âge adult

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

The relative timing of VMO and VL in the aetiology of anterior knee pain: a systematic review and meta-analysis

Background: Anterior knee pain (AKP) is a common musculoskeletal complaint. It has been suggested that one factor that may contribute to the presence of AKP is a delay in the recruitment of the vastus medialis oblique muscle (VMO) relative to the vastus lateralis muscle (VL). There is however little consensus within the literature regarding the existence or nature of any such delay in the recruitment of the VMO within the AKP population. The purpose of this systematic review and meta-analysis was to examine the relative timing of onset of the VMO and VL in those with AKP in comparison to the asymptomatic population.  Methods: The bibliographic databases AMED, British Nursing Index, CINAHL, EMBASE, Ovid Medline, PEDro, Pubmed and the Cochrane Library were searched for studies comparing the timing of EMG onset of the VMO and VL in those with AKP versus the asymptomatic population. Studies fulfilling the inclusion criteria were independently assessed. Heterogeneity across the studies was measured. A meta-analysis of results was completed for those studies where adequate data was supplied. Where comparable methodologies had been used, results were pooled and analysed.  Results: Fourteen studies met the inclusion criteria; one prospective and thirteen observational case control. Eleven compared VMO and VL EMG onset times during voluntary active tasks while four investigated reflex response times. All used convenience sampling and did not state blinding of the assessor. Study methodologies/testing and assessment procedures varied and there was considerable heterogeneity within individual samples. Whilst a trend was identified towards a delay in onset of VMO relative to the VL in the AKP population during both voluntary active tasks and reflex activity, a substantial degree of heterogeneity across the pooled studies was identified (I2 = 69.9–93.4%, p < 0.01).  Conclusion: Findings are subject to substantial and unexplained heterogeneity. A trend was demonstrated towards a delayed onset of VMO relative to VL in those with AKP in comparison to those without. However not all AKP patients demonstrate a VMO-VL dysfunction, and this is compounded by normal physiological variability in the healthy population. The clinical and therapeutic significance is therefore difficult to assess