Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures
Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures
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GABA能突触的小胶质细胞移位是复杂热性惊厥期间的保护性事件
DOI：
10.1016/j.celrep.2020.108346
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发表时间：
2020-11-03
期刊：
影响因子：
8.8
通讯作者：
Hu, Weiwei
中科院分区：
文献类型：
--
作者：
Wan, Yushan;Feng, Bo;Hu, Weiwei
复杂的热性惊厥(FSS)在成年期导致顽固性颞叶癫痫的高风险，然而复杂FSS的病理过程在很大程度上是未知的。在这里，我们证明了激活的小胶质细胞广泛地与谷氨酸能神经元胞体移位周围的GABA能前突触在复杂的FSS。膜片钳电生理学证实，GABA能突触前的小胶质细胞移位可以消除复合FS引起的GABA能神经传递和神经元兴奋性的增加，而GABA在这一未成熟阶段发挥兴奋作用。药物抑制GABA能突触前小胶质细胞移位或选择性消融CD11b(DTR)小胶质细胞可促进复杂FSS的产生。阻断或删除P2Y(12)受体(P2Y(12)R)可减少GABA能突触前小胶质细胞的移位，缩短复杂FSS的潜伏期。总之，受P2Y(12)R调节的GABA能前突触的小胶质细胞移位降低了神经元的兴奋性，从而促进了复杂FSS的产生。小胶质细胞移位是复杂性FSS病理过程中的一种保护性事件。
Complex febrile seizures (FSs) lead to a high risk of intractable temporal lobe epilepsy during adulthood, yet the pathological process of complex FSs is largely unknown. Here, we demonstrate that activated microglia extensively associated with glutamatergic neuronal soma displace surrounding GABAergic presynapses in complex FSs. Patch-clamp electrophysiology establishes that the microglial displacement of GABAergic presynapses abrogates a complex-FS-induced increase in GABAergic neurotransmission and neuronal excitability, whereas GABA exerts an excitatory action in this immature stage. Pharmacological inhibition of microglial displacement of GABAergic presynapses or selective ablation of microglia in CD11b(DTR) mice promotes the generation of complex FSs. Blocking or deleting the P2Y(12) receptor (P2Y(12)R) reduces microglial displacement of GABAergic presynapses and shortens the latency of complex FSs. Together, microglial displacement of GABAergic presynapses, regulated by P2Y(12)R, reduces neuronal excitability tomitigate the generation of complex FSs. Microglial displacement is a protective event during the pathological process of complex FSs.