Metabolic contributions to neuronal deficits caused by genomic disruption of schizophrenia risk gene SETD1A.

ABSTRACT: Regulation of neuronal metabolism during early brain development is crucial for directing synaptic plasticity and proper circuit formation. Alterations in neuronal glycolysis or mitochondrial function are associated with several neuropsychiatric disorders, including schizophrenia. Recently, loss-of-function mutations in SETD1A, a histone methyltransferase, have been linked to increased schizophrenia risk and global developmental delay. Here, we show that heterozygous disruption of SETD1A in human induced pluripotent stem cell (hiPSC)-derived neurons results in reduced neurite outgrowth and spontaneous activity, two phenotypes commonly associated with schizophrenia, as well as alterations in metabolic capacity. Furthermore, supplementing culture media with metabolic intermediates ameliorate

SUBMITTER: Chong ZS 

PROVIDER: S-EPMC9800576 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature