Akt and AMPK activators rescue hyperexcitability in neurons from patients with bipolar disorder.

ABSTRACT:

Background

Bipolar disorder (BD) is a multifactorial psychiatric illness affecting ∼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive.

Methods

In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies.

Findings

We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with chang

SUBMITTER: Khayachi A 

PROVIDER: S-EPMC11134542 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature