Impact of Sex Differences in Oligodendrocytes and Their Progenitor Cells on the Pathophysiology of Neuropsychiatric Disorders

Abstract

Department of Physiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Neuropsychiatric disorders such as multiple sclerosis, Alzheimer’s disease, and autism spectrum disorder exhibit significant sex differences in prevalence, progression, and response to treatment. Emerging evidence suggests that oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs) play pivotal roles in these pathologies via mechanisms involving neuroinflammation, energy metabolism, and hormonal modulation, resulting in distinct functional outcomes. Specifically, female OPCs display higher proliferative and migratory capacities, whereas male OPCs are more prone to differentiation and myeli-nation, thus contributing to robust myelin integrity. Dysregulation of these cells disrupts myelination and exacerbates disease progression. Addressing sex-specific gene expression in OPCs and OLs is therefore considered crucial for the development of targeted therapeutic strategies. This review highlights the significance of sex differences in the proliferation and differentiation of OPCs, as well as gene expression changes in OPCs and OLs, and emphasizes their contribution to the pathophysiology of neuropsy-chiatric disorders. Improved understanding of these differences is vital for advancing personalized sex-specific treatments and improving the clinical outcomes of neuropsychiatric disorders. (J Nippon Med Sch 2025; 92: 226―233).