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.
Original language | English |
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Article number | 10865 |
Journal | Nature Communications |
Volume | 15 |
DOIs | |
Publication status | Published - 30 Dec 2024 |
Funding
This work was supported by grants from the National Institutes of Health (5R01MH121544 to M.N.R.) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.N.R. and E.P.), and the US-Israel Binational Science Foundation (M.N.R. and E.P.). This project was also supported in part by the Genomic and RNA Profiling Core at Baylor College of Medicine with funding from the NIH S10 grant (1S10OD023469).
All Science Journal Classification (ASJC) codes
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology
- General Physics and Astronomy