Chronic haloperidol exposure impairs neurodevelopment via Notch1 signaling in human stem cell-derived brain organoids.

ABSTRACT: Haloperidol is a typical antipsychotic used to treat schizophrenia and induces dopamine D2 receptor antagonism. Long-term use of haloperidol can reduce brain size in animals and humans; however, the underlying mechanism of this effect remains unclear. Notch1 signaling regulates the development and function of the nervous system by balancing stem cell proliferation and differentiation. Therefore, we investigated the effects of long-term exposure to haloperidol on human-derived brain organoids, which served as sophisticated in vitro models of human brain development. Long-term exposure to haloperidol reduced the size of brain organoids and decreased the ventricular zone and Notch1 signaling. When propionate, which protects against haloperidol-induced toxicity, was combined with haloperidol,

SUBMITTER: Kang H 

PROVIDER: S-EPMC12271458 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature