美国西奈山伊坎医学院Anne Schaefer团队发现小胶质细胞对神经元活动的负反馈控制。这一研究成果于2020年9月30日发表在国际顶尖学术期刊《自然》。
他们显示小胶质细胞是小鼠神经元活动和相关行为反应的关键调节剂。小胶质细胞通过抑制神经元的活动来响应神经元的活动，而小胶质细胞的敲除会放大并同步神经元的活动，从而导致癫痫发作。小胶质细胞对神经元活动的抑制具有高度区域特异性，并且取决于小胶质细胞感知和分解代谢细胞外ATP的能力，后者在神经元和星形胶质细胞激活神经元后释放。
ATP触发小胶质细胞突起的募集，并由小胶质细胞ATP / ADP水解胞外酶CD39转化为AMP。然后，AMP通过CD73转化为腺苷，在小胶质细胞以及其他脑细胞上表达。ATP的小胶质细胞感应，随之而来的小胶质细胞依赖性腺苷生成，以及通过腺苷受体A1R进行腺苷介导的神经元反应抑制，对调节神经元活动和动物行为至关重要。
他们的研究结果表明，这种由小胶质细胞驱动的负反馈机制的运作方式与抑制性神经元相似，对于保护大脑免受健康和疾病的过度激活至关重要。
据了解，小胶质细胞是大脑中的常驻巨噬细胞，它通过去除垂死的神经元，修剪无功能的突触并产生支持神经元存活的配体来帮助调节大脑功能。
附：英文原文
Title: Negative feedback control of neuronal activity by microglia
Author: Ana Badimon, Hayley J. Strasburger, Pinar Ayata, Xinhong Chen, Aditya Nair, Ako Ikegami, Philip Hwang, Andrew T. Chan, Steven M. Graves, Joseph O. Uweru, Carola Ledderose, Munir Gunes Kutlu, Michael A. Wheeler, Anat Kahan, Masago Ishikawa, Ying-Chih Wang, Yong-Hwee E. Loh, Jean X. Jiang, D. James Surmeier, Simon C. Robson, Wolfgang G. Junger, Robert Sebra, Erin S. Calipari, Paul J. Kenny, Ukpong B. Eyo, Marco Colonna, Francisco J. Quintana, Hiroaki Wake, Viviana Gradinaru, Anne Schaefer
Issue&Volume: 2020-09-30
Abstract: Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival1. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A1R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease. Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.
DOI: 10.1038/s41586-020-2777-8
Source: https://www.nature.com/articles/s41586-020-2777-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
