Cortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability.

ABSTRACT: Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions using induced pluripotent stem cell (iPSC)-derived cortical- and hippocampal-ganglionic eminence assembloids to model developmental and epileptic encephalopathy 13, a condition arising from gain-of-function mutations in the SCN8A gene encoding the sodium channel Nav1.6. While cortical assembloids showed network hyperexcitability akin to epileptogenic tissue, hippocampal assembloids did not, and instead displayed network dysregulation patterns similar to in vivo hippo

SUBMITTER: McCrimmon CM 

PROVIDER: S-EPMC12674601 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature