Impaired neural stress resistance and loss of REST in bipolar disorder.

ABSTRACT: Neurodevelopmental changes and impaired stress resistance have been implicated in the pathogenesis of bipolar disorder (BD), but the underlying regulatory mechanisms are unresolved. Here we describe a human cerebral organoid model of BD that exhibits altered neural development, elevated neural network activity, and a major shift in the transcriptome. These phenotypic changes were reproduced in cerebral organoids generated from iPS cell lines derived in different laboratories. The BD cerebral organoid transcriptome showed highly significant enrichment for gene targets of the transcriptional repressor REST. This was associated with reduced nuclear REST and REST binding to target gene recognition sites. Reducing the oxygen concentration in organoid cultures to a physiological range ameliorate

SUBMITTER: Meyer K 

PROVIDER: S-EPMC11964151 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature