D'Angelo Martina, Di Stefano Valeria, Pullano Ilaria, Monaco Francesco, Steardo Luca
Department of Health Sciences, University of Catanzaro Magna Graecia, 88100 Catanzaro, Italy.
Department of Mental Health, Azienda Sanitaria Locale Salerno, 84132 Salerno, Italy.
Life (Basel). 2025 Jun 6;15(6):921. doi: 10.3390/life15060921.
Oligodendrocyte precursor cells (OPCs) are a dynamic and heterogeneous population of glial cells essential for brain development and myelination. Beyond their well-established role in oligodendrogenesis, emerging evidence suggests that OPCs contribute to synaptic regulation, neuronal communication, and brain plasticity. Recent studies have increasingly implicated OPC dysfunction in the pathophysiology of psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). This narrative review integrates clinical, genetic, transcriptomic, and histological findings to examine the role of OPC alterations in mental illnesses. In SCZ, OPC abnormalities predominantly affect myelination, but recent data also suggest deficits in non-canonical functions, including neuron-OPC communication. Findings in BD largely mirror those in SCZ, implying shared OPC-related mechanisms across these disorders. In contrast, OPC involvement in MDD appears more complex, with evidence supporting both myelination deficits and non-canonical dysfunctions, such as impaired neuro-glial interactions and perineuronal network alterations. The developmental timing of OPC dysfunction may represent a common denominator underlying psychiatric disorders, as early-life stress and neurodevelopmental disturbances have been linked to OPC impairments. Moreover, given the shared developmental origins of OPCs and parvalbumin-positive interneurons, disruptions in their mutual interactions may contribute to broader neural network dysregulation. Despite these insights, the field remains in its infancy. Future studies integrating independent human cohorts with robust preclinical models are needed to clarify the extent of OPC involvement in psychiatric pathophysiology. Understanding OPC dysfunction may reveal novel biomarkers and open new avenues for individualized therapeutic interventions and preventive strategies in mental health.
少突胶质前体细胞（OPCs）是一类动态且异质性的神经胶质细胞群体，对大脑发育和髓鞘形成至关重要。除了在少突胶质细胞生成中已确立的作用外，新出现的证据表明，OPCs有助于突触调节、神经元通讯和大脑可塑性。最近的研究越来越多地表明，OPC功能障碍与精神疾病的病理生理学有关，尤其是精神分裂症（SCZ）、双相情感障碍（BD）和重度抑郁症（MDD）。这篇叙述性综述整合了临床、遗传、转录组学和组织学研究结果，以探讨OPC改变在精神疾病中的作用。在SCZ中，OPC异常主要影响髓鞘形成，但最近的数据也表明非经典功能存在缺陷，包括神经元与OPC的通讯。BD的研究结果在很大程度上与SCZ相似，这意味着这些疾病存在共同的与OPC相关的机制。相比之下，OPC在MDD中的参与似乎更为复杂，有证据支持髓鞘形成缺陷和非经典功能障碍，如神经胶质相互作用受损和神经元周围网络改变。OPC功能障碍的发育时间可能是精神疾病的一个共同特征，因为早期生活压力和神经发育障碍与OPC损伤有关。此外，鉴于OPC和小白蛋白阳性中间神经元具有共同的发育起源，它们相互作用的破坏可能导致更广泛的神经网络失调。尽管有这些见解，但该领域仍处于起步阶段。未来需要将独立的人类队列与强大的临床前模型相结合的研究，以阐明OPC在精神疾病病理生理学中的参与程度。了解OPC功能障碍可能会揭示新的生物标志物，并为心理健康的个体化治疗干预和预防策略开辟新途径。
