Kato Daisuke
Department of Physiology, Graduate School of Medicine, Nippon Medical School.
J Nippon Med Sch. 2025;92(3):226-233. doi: 10.1272/jnms.JNMS.2025_92-306.
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 myelination, 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 neuropsychiatric disorders. Improved understanding of these differences is vital for advancing personalized sex-specific treatments and improving the clinical outcomes of neuropsychiatric disorders.
多发性硬化症、阿尔茨海默病和自闭症谱系障碍等神经精神疾病在患病率、病程进展及对治疗的反应方面存在显著的性别差异。新出现的证据表明，少突胶质细胞（OLs）和少突胶质前体细胞（OPCs）通过涉及神经炎症、能量代谢和激素调节的机制在这些疾病中发挥关键作用，从而导致不同的功能结果。具体而言，雌性OPCs表现出更高的增殖和迁移能力，而雄性OPCs更易于分化和髓鞘形成，从而有助于维持强大的髓鞘完整性。这些细胞的失调会破坏髓鞘形成并加剧疾病进展。因此，解决OPCs和OLs中的性别特异性基因表达问题被认为对制定靶向治疗策略至关重要。本综述强调了OPCs增殖和分化中性别差异的重要性，以及OPCs和OLs中的基因表达变化，并强调了它们对神经精神疾病病理生理学的贡献。更好地理解这些差异对于推进个性化的性别特异性治疗以及改善神经精神疾病的临床结果至关重要。
