Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Studies on the mechanosensitive ion channel Piezo2 largely focus on its role in the peripheral nervous system, particularly in touch and pain sensation. Here, we investigate Piezo2 function in the anterior visual pathway of the central nervous system with a focus on oligodendrocyte (OL) biology and myelin integrity. Using single-nucleus RNA sequencing, we identifyexpression in late differentiated OLs of the murine optic nerve, with minor expression in retinal ganglion cells. OL-specificdeficiency results in age-dependent motor impairment and selective disruption of myelin compaction in small-caliber optic nerve axons, a fiber population known to be particularly vulnerable in demyelinating disease. Differential gene expression analysis further indicates that Piezo2 regulates myelin compaction and white matter integrity in mature OLs. Consistent with these findings, OL-encodedexpression is reduced in optic nerve lesion areas from multiple sclerosis patients, highlighting a convergent mechanism of small-caliber fiber vulnerability. Together, these data identify Piezo2 as an age-related regulator of OL function and myelin integrity, with potential relevance for preserving white matter structure in multiple sclerosis. Abs1 Oligodendroglial Piezo2 is shown to regulate myelin compaction in small optic nerve axons. Its downregulation in multiple sclerosis suggests Piezo2 as a therapeutic target to support white matter integrity in chronic inflammation. Abs2 web-summary