小膠質細胞負反饋控制神經元活動
作者：
小柯機器人發布時間：2020/10/2 23:35:22
美國西奈山伊坎醫學院Anne Schaefer團隊發現小膠質細胞對神經元活動的負反饋控制。這一研究成果於2020年9月30日發表在國際頂尖學術期刊《自然》。
他們顯示小膠質細胞是小鼠神經元活動和相關行為反應的關鍵調節劑。小膠質細胞通過抑制神經元的活動來響應神經元的活動，而小膠質細胞的敲除會放大並同步神經元的活動，從而導致癲癇發作。小膠質細胞對神經元活動的抑制具有高度區域特異性，並且取決於小膠質細胞感知和分解代謝細胞外ATP的能力，後者在神經元和星形膠質細胞激活神經元後釋放。
ATP觸發小膠質細胞突起的募集，並由小膠質細胞ATP / ADP水解胞外酶CD39轉化為AMP。然後，AMP通過CD73轉化為腺苷，在小膠質細胞以及其他腦細胞上表達。ATP的小膠質細胞感應，隨之而來的小膠質細胞依賴性腺苷生成，以及通過腺苷受體A1R進行腺苷介導的神經元反應抑制，對調節神經元活動和動物行為至關重要。
他們的研究結果表明，這種由小膠質細胞驅動的負反饋機制的運作方式與抑制性神經元相似，對於保護大腦免受健康和疾病的過度激活至關重要。
據了解，小膠質細胞是大腦中的常駐巨噬細胞，它通過去除垂死的神經元，修剪無功能的突觸並產生支持神經元存活的配體來幫助調節大腦功能。
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