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Publication : Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.

First Author  Ding X Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  10865
PubMed ID  39738113 Mgi Jnum  J:360644
Mgi Id  MGI:7798321 Doi  10.1038/s41467-024-55209-7
Citation  Ding X, et al. (2024) Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG. Nat Commun 15(1):10865
abstractText  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.
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