Search results for "Mental disorder"

The neuroanatomy of Eml1 knockout mice, a model of subcortical heterotopia

2018

Symposium issue: Human Cortex Developmentidentifiant wos: 000482426800014; International audience; The cerebral cortex is a highly organized structure responsible for advanced cognitive functions. Its development relies on a series of steps including neural progenitor cell proliferation, neuronal migration, axonal outgrowth and brain wiring. Disruption of these steps leads to cortical malformations, often associated with intellectual disability and epilepsy. We have generated a new resource to shed further light on subcortical heterotopia, a malformation characterized by abnormal neuronal position. We describe here the generation and characterization of a knockout (KO) mouse model for Eml1,…

Activation of MORs in the VTA induces changes on cFos expression in different projecting regions: Effect of inflammatory pain.

2019

Abstract Chronic pain is a worldwide major health problem and many pain-suffering patients are under opioid based therapy. Epidemiological data show that pain intensity correlates with the risk of misuse of prescription opioids, and other drugs of abuse including alcohol. This increased vulnerability to suffer Substance Use Disorders could be, in part, caused by functional changes that occur over the mesocorticolimbic system, a brain pathway involved in reward processing and addiction. Previous data in rats revealed that inflammatory pain desensitizes mu opioid receptors (MORs) in the ventral tegmental area (VTA). As a consequence, pain alters dopamine release in the nucleus accumbens (NAc)…

Delirium Predisposing and Triggering Factors in Nursing Home Residents: A Cohort Trial-Nested Case-Control Study.

2019

Background Delirium is a common geriatric syndrome, with a prevalence of between 15-70% among older long-term care residents. It is associated with adverse outcomes, and its onset may prove imperceptible to health professionals. Few studies in institutionalized older people have analyzed the predictors of delirium. Objective The aim of the present study was to identify delirium predisposing and triggering factors, and develop a predictive model. Methods A cohort trial-nested case-control study covering a period of 12 consecutive months (April 2015 - March 2016) was carried out. Predisposing and triggering episodes of delirium were recorded. Results A total of 443 older persons were recruite…

Left hemisphere enhancement of auditory activation in language impaired children

2019

| openaire: EC/H2020/641652/EU//ChildBrain Specific language impairment (SLI) is a developmental disorder linked to deficient auditory processing. In this magnetoencephalography (MEG) study we investigated a specific prolonged auditory response (N250m) that has been reported predominantly in children and is associated with level of language skills. We recorded auditory responses evoked by sine-wave tones presented alternately to the right and left ear of 9–10-year-old children with SLI (n = 10) and children with typical language development (n = 10). Source analysis was used to isolate the N250m response in the left and right hemisphere. In children with language impairment left-hemisphere …

Acute and chronic nicotine exposures differentially affect central serotonin 2A receptor function : focus on the lateral habenula

2020

Nicotine addiction is a serious public health problem causing millions of deaths worldwide. Serotonin (5-hydroxytryptamine

Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations.

2016

Methyl-CpG binding protein 2 (MeCP2) is a widely abundant, multifunctional protein most highly expressed in post-mitotic neurons. Mutations causing Rett syndrome and related neurodevelopmental disorders have been identified along the entire MECP2 locus, but symptoms vary depending on mutation type and location. C-terminal mutations are prevalent, but little is known about the function of the MeCP2 C-terminus. We employ the genetic efficiency of Drosophila to provide evidence that expression of p.Arg294* (more commonly identified as R294X), a human MECP2 E2 mutant allele causing truncation of the C-terminal domains, promotes apoptosis of identified neurons in vivo. We confirm this novel find…

2018

Photobacterium damselae subsp. damselae (Pdd) is an emerging pathogen of marine animals that sometimes causes serious infections in humans. Two related pore forming toxins, phobalysins P and C, and damselysin, a phospholipase D, confer strong virulence of Pdd in mice. Because infections by Pdd are typically caused following exposure of wounds to sea water we investigated how salinity impacts toxin activity, swimming, and association of Pdd with epithelial cells. These activities were low when bacteria were pre-cultured in media with 3.5% NaCl, the global average salinity of sea water. In contrast, lower salinity increased swimming of wild type Pdd peaking at 2% NaCl, hemolysis, and associat…

The broad phenotypic spectrum of PPP2R1A -related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

2021

PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay …

Beyond protein-coding genes

2019

A long non-coding RNA called lnc-NR2F1 regulates several neuronal genes, including some involved in autism and intellectual disabilities.

Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their p…

2020

IntroductionThe Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with ‘Mental Retardation Autosomal Dominant 57’ (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies.MethodsWe re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and…