小清蛋白中间神经元损伤可能是精神分裂症发生发展的中心环节

Parvalbumin Interneuron Damage Plays a Central Role in the Pathogenesis of Schizophrenia

摘要: 小清蛋白中间神经元(parvalbumin interneuron, PVI)是一种具有长期发育轨迹的神经元群体，容易受到出生后危险因素的影响和伤害。本文系统复习了可能导致PVI损伤的危险因素，包括多巴胺能系统亢进、NMDA受体被阻断和氧化应激。这些因素均在精神分裂症的疾病发生中起重要作用。损伤的PVI对其下游的神经元活动调控障碍，使中脑腹侧被盖区多巴胺能神经元去抑制因而皮层多巴胺释放增加、谷氨酸脱抑制性释放产生兴奋性神经毒性、并影响少突胶质前体细胞(OPC)发育和成熟因而出现髓鞘化障碍。通过这些途径，PVI损伤影响脑高级功能活动，包括认知、情感和社会功能障碍。

Abstract: Parvalbumin interneurons (PVIs) are featured with a long developmental trajectory. They are sen-sitive and susceptible to risk factors in the postnatal life. This article made a systemic review on the risk factors including dopaminergic hyperfunction, blockade of NMDA receptors, and oxidative stress. These risk factors are also involved in the pathogenesis of schizophrenia. Damaged PVIs are unable to effectively regulate their post-synaptic neurons and subsequently result in various out-comes exemplified as elevated dopamine release in cerebral cortex subsequent to the dis-inhibition on dopaminergic neurons in ventral tegmental area of the midbrain, higher levels of glutamate, which is neurotoxicity, resulting from dis-inhibition on glutamatergic neurons, and myelination deficit due to delayed development of oligodendrocyte precursor cells (OPCs) into matured oli-godendrocytes in the brain. Via the above mechanisms, PVI damage may impair the higher brain functions such as cognition, emotion, and sociability in humans thus playing a central role in the pathogenesis of schizophrenia.