Language

English

Publication Date

12-30-2024

Journal

Nature Communications

DOI

10.1038/s41467-024-55209-7

PMID

39738113

PMCID

PMC11686269

PubMedCentral® Posted Date

12-30-2024

PubMedCentral® Full Text Version

Post-print

Abstract

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In addition, these mice exhibit significant histological, electrophysiological, and behavioral pathophysiologies. Unbiased translatomic profiling reveals potential compensatory machineries. These results highlight the functions of glial AnkG in maintaining proper axoglial interactions throughout aging and suggest a contribution of glial AnkG to neuropsychiatric disorders.

Keywords

Animals, Oligodendroglia, Mice, Knockout, Mice, Ankyrins, Aging, Bipolar Disorder, Axons, Male, Neuroglia, Mice, Inbred C57BL, Female, Behavior, Animal, Neurons, Oligodendrocyte, Molecular neuroscience

Published Open-Access

yes

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