Mordelt Annika, de Witte Lot D
Department of Human Genetics and Department of Cognitive Neuroscience, Radboudumc, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Nijmegen, the Netherlands.
Department of Human Genetics and Department of Cognitive Neuroscience, Radboudumc, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Nijmegen, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Curr Opin Neurobiol. 2023 Apr;79:102674. doi: 10.1016/j.conb.2022.102674. Epub 2023 Jan 17.
There is a consensus in the field that microglia play a prominent role in neurodevelopmental processes like synaptic pruning and neuronal network maturation. Thus, a current momentum of associating microglia deficits with neurodevelopmental disorders (NDDs) emerged. This concept is challenged by rodent studies and clinical data. Intriguingly, reduced numbers of microglia or altered microglial functions do not necessarily lead to overt NDD phenotypes, and neuropsychiatric symptoms seem to develop primarily in adulthood. Hence, it remains open for discussion whether microglia are truly indispensable for healthy neurodevelopment. Here, we critically discuss the role of microglia in synaptic pruning and highlight area- and age dependency. We propose an updated model of microglia-mediated synaptic pruning in the context of NDDs and discuss the potential of targeting microglia for treatment of these disorders.
该领域已形成一种共识，即小胶质细胞在诸如突触修剪和神经网络成熟等神经发育过程中发挥着重要作用。因此，目前出现了将小胶质细胞缺陷与神经发育障碍（NDDs）联系起来的趋势。这一概念受到了啮齿动物研究和临床数据的挑战。有趣的是，小胶质细胞数量减少或其功能改变并不一定会导致明显的NDD表型，而且神经精神症状似乎主要在成年期出现。因此，小胶质细胞对于健康的神经发育是否真的不可或缺，仍有待讨论。在这里，我们批判性地讨论了小胶质细胞在突触修剪中的作用，并强调了区域和年龄依赖性。我们提出了一个在NDD背景下小胶质细胞介导的突触修剪的更新模型，并讨论了针对小胶质细胞治疗这些疾病的潜力。
