Year: 2024
Type: article
Abstract: Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.
Source: Scientific Reports
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Awards: "ENDOGENOUS PARVOVIRAL ELEMENTS IN MAMMALIAN GENOMES DISSECTING THE CELLULAR FUNCTION OF INTACT NS1/REP DERIVED GENES", POSTSYNAPTIC 5-HT2 RECEPTOR SUBTYPES MODULATE EXCITATORY SYNAPTIC TRANSMISSION IN THE MEDIAL PREFRONTAL CORTEX, G2291568336, PLATAFORMA AUTOMATIZADA DE DPCR PARA ANALISIS CUANTITATIVOS ABSOLUTOS, G2759144041, G3175981791, NEUROMODULATION BY 5-HT AT CENTRAL SYNAPSES, G4466356285, DISCOVERING THE METABOLIC PATHWAY THAT MEDIATES THE SYNTHESIS AND DEGRADATION OF INORGANIC POLYPHOSPHATE CHAINS IN THE CENTRAL NERVOUS SYSTEM CRITICAL ROLE IN THE ONSET AND PROGRESSION OF NEURODEGENERATIVE DISEASES., VISUALIZACION DE PROTEINAS SINAPTICA MEDIANTE EL USO DE UN MICROSCOPIO DE DOS FOTONES., POST-TRANSLATIONAL REGULATION OF WNT RECEPTORS IN ADULT NEURAL PROGENITOR CELLS, LABORATORIO DE TECNOLOGIAS DE EDICION DEL GENOMA PARA MODELAR ENFERMEDADES NEURODEGENERATIVAS EN MODELOS MURINOS, A NEW MODEL OF AUTISM SPECTRUM DISORDER ROLE OF SYNAPTIC VESICLE ACIDIFICATION DEFECTS ON SYNAPTIC TRANSMISSION AND ANIMAL BEHAVIORS.
OpenAlex ID: W4402120620