Center for Neuroscience, University of California at Davis, Davis, California.
Biol Psychiatry. 2014 Feb 15;75(4):262-8. doi: 10.1016/j.biopsych.2013.10.003. Epub 2013 Oct 10.
Although the etiology of schizophrenia (SZ) remains unknown, it is increasingly clear that immune dysregulation plays a central role. Genome-wide association studies reproducibly indicate an association of SZ with immune genes within the major histocompatibility complex (MHC). Moreover, environmental factors that increase risk for SZ, such as maternal infection, alter peripheral immune responses as well as the expression of immune molecules in the brain. MHC class I (MHCI) molecules might mediate both genetic and environmental contributions to SZ through direct effects on brain development in addition to mediating immunity. MHCI molecules are expressed on neurons in the central nervous system throughout development and into adulthood, where they regulate many aspects of brain development, including neurite outgrowth, synapse formation and function, long-term and homeostatic plasticity, and activity-dependent synaptic refinement. This review summarizes our current understanding of MHCI expression and function in the developing brain as well as its involvement in maternal immune activation, from the perspective of how these roles for MHCI molecules might contribute to the pathogenesis of SZ.
虽然精神分裂症（SZ）的病因仍然未知，但越来越清楚的是，免疫失调起着核心作用。全基因组关联研究反复表明，SZ 与主要组织相容性复合体（MHC）内的免疫基因有关。此外，增加 SZ 风险的环境因素，如母体感染，改变外周免疫反应以及大脑中免疫分子的表达。MHC Ⅰ类（MHCI）分子可能通过直接影响大脑发育，在遗传和环境对 SZ 的贡献中发挥中介作用，除了介导免疫之外。MHCI 分子在中枢神经系统的神经元中表达，从发育到成年，它们调节大脑发育的许多方面，包括神经突生长、突触形成和功能、长期和动态可塑性以及活动依赖性突触细化。从这些 MHCI 分子的作用如何有助于 SZ 的发病机制的角度，本文综述了我们目前对发育中大脑中 MHCI 表达和功能及其在母体免疫激活中的作用的理解。
