CASPR2 Autoimmune Antibodies Induce Neuronal Hyperactivity in Human Brain Organoids.

ABSTRACT: Gestational transfer of brain-reactive antibodies is a risk factor for neurodevelopmental disorders. Contactin-associated protein-like 2 (CASPR2) is a known target for pathogenic maternal autoantibodies which have been proposed to interfere with fetal neurodevelopment. However, the impact of CASPR2 antibodies on human brain development remains largely unknown. Here, to better understand the neurophysiological changes that occur in the presence of these pathogenic autoantibodies, we cultured unguided human neural organoids for a period of 6-months in media containing anti-CASPR2 antibodies. We then performed neurophysiological characterization via whole-cell patch-clamp and calcium imaging in acute organoid slices. Our results reveal that CASPR2 antibody exposure increased spontaneous synap

SUBMITTER: Oliveira AR 

PROVIDER: S-EPMC12926859 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature