Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases.

ABSTRACT: The neuro-physiological properties of individuals with genetic pre-disposition to neurological disorders are largely unknown. Here we aimed to explore these properties using cerebral organoids (COs) derived from fibroblasts of individuals with confirmed genetic mutations including PRNP^E200K, trisomy 21 (T21), and LRRK2^G2019S, which are associated with Creutzfeldt Jakob disease, Down Syndrome, and Parkinson's disease. We utilized no known disease/healthy COs (HC) as normal function controls. At 3-4 and 6-10 months post-differentiation, COs with mutations showed no evidence of disease-related pathology. Electrophysiology assessment showed that all COs exhibited mature neuronal firing at 6-10 months old. At this age, we observed significant changes in the electrophysiolo

SUBMITTER: Foliaki ST 

PROVIDER: S-EPMC8507222 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature