PDF(Pubmed)
Abstract：
Microglia are the brain\'s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.
摘要：
小胶质细胞是大脑的常驻巨噬细胞,指导对大脑成熟至关重要的各种发育过程，活动,和可塑性。小胶质细胞祖细胞在受孕后第4周进入端脑壁，并以时空跟踪人类关键神经发育过程的方式定植胎儿大脑。然而,我们所知道的关于小胶质细胞如何塑造神经发育的大部分来自啮齿动物的研究。人类和啮齿动物小胶质细胞之间存在多种差异，需要进一步关注人类状况。特别是小胶质细胞正在成为各种认知和神经发育障碍的重要病理标志。在这篇文章中,我们通过关注人类物种，回顾了支持小胶质细胞参与基本神经发育过程的证据。接下来，我们同意神经病理学证据，证明小胶质细胞是否以及如何导致两种神经发育障碍的病因：自闭症谱系疾病和精神分裂症。接下来,我们强调了最近的技术如何彻底改变了我们对小胶质细胞生物学的理解，重点是这些工具如何帮助我们以前所未有的分辨率阐明小胶质细胞和神经发育障碍之间的联系。最后，我们回顾了当前哪些治疗方法在神经发育障碍中对靶向小胶质细胞最有希望，并提出了未来考虑的新途径。
