Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.
Xiaoyun DingYu WuVictoria RodriguezEmily RiccoJames T OkohYanhong LiuDaniel C KraushaarMatthew N RasbandPublished in: bioRxiv : the preprint server for biology (2024)
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 generated oligodendroglia-specific AnkG conditional knockout mice and observed the destabilization of axoglial interactions in aged but not young adult mice. In addition, these mice exhibited profound histological, electrophysiological, and behavioral pathophysiologies. Unbiased translatomic profiling revealed potential compensatory machineries. These results highlight the critical functions of glial AnkG in maintaining proper axoglial interactions throughout aging and suggests a previously unrecognized contribution of oligodendroglial AnkG to neuropsychiatric disorders.
Keyphrases
- bipolar disorder
- high fat diet induced
- single cell
- young adults
- spinal cord
- neuropathic pain
- gene expression
- intellectual disability
- early stage
- radiation therapy
- autism spectrum disorder
- small molecule
- skeletal muscle
- blood brain barrier
- transcription factor
- protein protein
- optical coherence tomography
- rectal cancer
- subarachnoid hemorrhage