Lukens John R, Eyo Ukpong B
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia, USA; email:
Center for Brain Immunology and Glia, University of Virginia, Charlottesville, Virginia, USA.
Annu Rev Neurosci. 2022 Jul 8;45:425-445. doi: 10.1146/annurev-neuro-110920-023056. Epub 2022 Apr 18.
Mounting evidence indicates that microglia, which are the resident immune cells of the brain, play critical roles in a diverse array of neurodevelopmental processes required for proper brain maturation and function. This evidence has ultimately led to growing speculation that microglial dysfunction may play a role in neurodevelopmental disorder (NDD) pathoetiology. In this review, we first provide an overview of how microglia mechanistically contribute to the sculpting of the developing brain and neuronal circuits. To provide an example of how disruption of microglial biology impacts NDD development, we also highlight emerging evidence that has linked microglial dysregulation to autism spectrum disorder pathogenesis. In recent years, there has been increasing interest in how the gut microbiome shapes microglial biology. In the last section of this review, we put a spotlight on this burgeoning area of microglial research and discuss how microbiota-dependent modulation of microglial biology is currently thought to influence NDD progression.
越来越多的证据表明,作为大脑中的常驻免疫细胞,小胶质细胞在大脑正常成熟和功能所需的一系列神经发育过程中发挥着关键作用。这一证据最终引发了越来越多的猜测,即小胶质细胞功能障碍可能在神经发育障碍(NDD)的病理病因中起作用。在这篇综述中,我们首先概述小胶质细胞如何在机制上促进发育中的大脑和神经元回路的塑造。为了举例说明小胶质细胞生物学的破坏如何影响NDD的发展,我们还强调了将小胶质细胞失调与自闭症谱系障碍发病机制联系起来的新证据。近年来,人们对肠道微生物群如何塑造小胶质细胞生物学越来越感兴趣。在这篇综述的最后一部分,我们重点关注这个小胶质细胞研究的新兴领域,并讨论目前认为微生物群依赖的小胶质细胞生物学调节如何影响NDD的进展。