Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.
Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.
复制标题
DOI：
10.1016/j.celrep.2018.02.004
复制
发表时间：
2018-02-20
期刊：
影响因子：
8.8
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Zhao X;Liao Y;Morgan S;Mathur R;Feustel P;Mazurkiewicz J;Qian J;Chang J;Mathern GW;Adamo MA;Ritaccio AL;Gruenthal M;Zhu X;Huang Y
众所周知，小胶质细胞在维持大脑稳态中起着至关重要的作用。然而，它们在癫痫发生中的作用尚未确定。在这里，我们证明了小鼠小胶质细胞中mTOR信号的升高会导致表型变化，包括变形虫样形态、增殖增加和强大的吞噬活性，但没有显著的促炎细胞因子诱导。我们进一步提供证据表明，这些小胶质细胞的非炎症性变化破坏了中枢神经系统的稳态，导致突触密度降低，小胶质细胞明显浸润到海马锥体层，中度神经元变性和星形胶质细胞的大量增殖。此外，受影响的小鼠出现严重的早发性自发性复发性癫痫发作（srs）。因此，我们揭示了一种独立于小胶质细胞炎症反应的致痫机制。我们的数据表明，小胶质细胞可能是预防癫痫的合适靶点。Zhao等人发现，小胶质细胞中mTOR信号的升高促使细胞获得非炎症反应样表型，从而导致中枢神经系统稳态的破坏。作者还报道，反应样小胶质细胞促进癫痫发生独立于炎症反应。
Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippo-campal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention. Zhao et al. reveal that elevated mTOR signaling in microglia propels the cells to acquire a noninflammatory reactive-like phenotype, which leads to disruption of CNS homeostasis. The authors also report that reactive-like microglia promote epileptogenesis independent of the inflammatory response.
登录
查看更多内容
影响因子：
5.6
作者：
Aronica E;Bauer S;Bozzi Y;Caleo M;Dingledine R;Gorter JA;Henshall DC;Kaufer D;Koh S;Löscher W;Louboutin JP;Mishto M;Norwood BA;Palma E;Poulter MO;Terrone G;Vezzani A;Kaminski RM
通讯作者：
Kaminski RM
Trasmembrane趋化因子CX3CL1和CXCL16在神经元，小胶质细胞和星形胶质细胞之间驱动相互作用，以抵消PMCAO和兴奋性神经元死亡。
影响因子：
5.3
作者：
Rosito M;Lauro C;Chece G;Porzia A;Monaco L;Mainiero F;Catalano M;Limatola C;Trettel F
通讯作者：
Trettel F
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
影响因子：
8.8
作者：
Shen K;Sidik H;Talbot WS
通讯作者：
Talbot WS
影响因子：
16.6
作者：
Matsuda, Taito;Murao, Naoya;Katano, Yuki;Juliandi, Berry;Kohyama, Jun;Akira, Shizuo;Kawai, Taro;Nakashima, Kinichi
通讯作者：
Nakashima, Kinichi