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Brpf1 regulates the function of MGE-derived GABAergic interneurons

         

摘要

Intellectual disability is a broad-spectrum neurodevelopmental disorder characterized by marked impairment of intelligence and adaptive function.Impaired GABA neurotransmission is associated with mental disorders such as epilepsy and mental retardation,and patients with BRPF1 mutations were mentally retarded and often accompanied by epilepsy.Our research is to investigate the role of Brpf1 in the development and function of GABAergic interneurons.We used mouse primary in vitro cultured GABAergic interneurons derived from medial ganglionic eminence(MGE)and utilized AAV-shBrpf1 virus to knockdown Brpf1.The results showed that Brpf1 knockdown led to increased threshold and decreased number of evoked action potentials,and a downward trend of the amplitude and frequency of mIPSC.However,Brpf1 knockdown had lttle effect on the differentiation of GABAergic interneurons as revealed by parvalbumin and somatostatin staining.Moreover,little influence on the morphology was observed as shown by MAP2 and Golgi stain.Finally,it was found that most of the up-regulated genes are involved in protein binding,ubiquitination,and inflammatory response by RNA Seq.

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