Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury.
Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury.
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DOI：
10.1084/jem.20172244
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发表时间：
2018-07-02
期刊：
影响因子：
--
通讯作者：
Kipnis J
中科院分区：
文献类型：
--
作者：
Norris GT;Smirnov I;Filiano AJ;Shadowen HM;Cody KR;Thompson JA;Harris TH;Gaultier A;Overall CC;Kipnis J
诺里斯等人。研究表明，小胶质细胞是视神经损伤后背外侧膝状核中突触碎片清除的关键吞噬细胞。这种小胶质细胞功能依赖于对神经变性的识别，并由补体系统介导。小胶质细胞对突触物质的吞噬作用对于中枢神经系统的发育至关重要。受伤的成人大脑中的小胶质细胞功能尚不清楚。小胶质细胞吞噬作用的测定具有挑战性，因为外周骨髓细胞植入损伤部位，这可能会模糊对小胶质细胞作用的解释。这里使用的模型，视神经挤压损伤，导致背外侧膝状核（dLGN）突触变性，这会刺激驻留小胶质细胞快速激活和吞噬突触物质，而无需骨髓细胞植入。小胶质细胞的药理耗竭导致损伤后突触碎片的积累，表明小胶质细胞是损伤后的主要吞噬细胞。遗传或药理学操作表明，损伤后神经元活动不会触发小胶质细胞的吞噬作用。 RNA 测序揭示 C1q 和 CD11b/CR3 参与 dLGN 驻留小胶质细胞清除碎片。事实上，C1qa−/− 和 Itgam−/− 小鼠表现出损伤后碎片清除能力受损。我们的结果显示了小胶质细胞如何清除神经退行性碎片，并为研究其机制和生理作用提供了模型。
Norris et al. show that microglia are the key phagocytes in removal of synaptic debris in the dorsal lateral geniculate nucleus after optic nerve injury. This microglial function is dependent on recognition of neurodegeneration and is mediated by the complement system. Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa−/− and Itgam−/− mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
2.5
作者：
Bartel, Dianna L.
通讯作者：
Bartel, Dianna L.
影响因子：
11.2
作者：
Butovsky, Oleg;Jedrychowski, Mark P.;Cialic, Ron;Krasemann, Susanne;Murugaiyan, Gopal;Fanek, Zain;Greco, David J.;Wu, Pauline M.;Doykan, Camille E.;Kiner, Olga;Lawson, Robert J.;Frosch, Matthew P.;Pochet, Nathalie;El Fatimy, Rachid;Krichevsky, Anna M.;Gygi, Steven P.;Lassmann, Hans;Berry, James;Cudkowicz, Merit E.;Weiner, Howard L.
通讯作者：
Weiner, Howard L.
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
11.4
作者：
Benhar, Inbal;Reemst, Kitty;Schwartz, Michal
通讯作者：
Schwartz, Michal