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Microglia depletion exacerbates acute seizures and hippocampal neuronal degeneration in mouse models of epilepsy.
American Journal of Physiology-Cell Physiology ( IF 5.0 ) Pub Date : 2020-08-12 , DOI: 10.1152/ajpcell.00205.2020
Mei Liu 1 , Lijuan Jiang 1 , Min Wen 1 , Yue Ke 1 , Xiangzhen Tong 1 , Weiyuan Huang 1 , Rongqing Chen 1, 2
Affiliation  

Epileptic seizures are the manifestation of hypersynchronous and excessive neuronal excitation. While the glutamatergic and GABAergic neurons play major roles in shaping fast neuronal excitation/inhibition homeostasis, it is well illustrated that astrocytes profoundly regulate neuronal excitation by controlling glutamate, GABA, cannabinoids, adenosine and concentration of K+ around neurons. However, little is known whether microglia take part in the regulation of acute neuronal excitation and ongoing epileptic behaviors. We proposed that if microglia are innately ready to respond to epileptic overexcitation, depletion of microglia might alter neuronal excitability and severity of acute epileptic seizures. We found that microglia depletion by PLX3397, an inhibitor of CSF1R, exacerbates seizure severity and excitotoxicity-induced neuronal degeneration, indicating that microglia are rapidly responsive to the change of excitation/inhibition homeostasis and participate in the protection of neurons from overexcitation.

中文翻译:

小胶质细胞耗竭加剧了癫痫小鼠模型的急性发作和海马神经元变性。

癫痫性癫痫发作是过度同步和过度神经元兴奋的表现。尽管谷氨酸能和GABA能神经元在快速神经元兴奋/抑制稳态中起主要作用,但充分说明,星形胶质细胞通过控制谷氨酸,GABA,大麻素,腺苷和K +的浓度来深刻调节神经元兴奋。在神经元周围。然而,鲜为人知的是小胶质细胞是否参与了急性神经元兴奋的调节和持续的癫痫行为。我们提出,如果小胶质细胞天生就准备好应对癫痫过度兴奋,小胶质细胞的耗竭可能会改变神经元兴奋性和急性癫痫发作的严重程度。我们发现,PLX3397(CSF1R抑制剂)对小胶质细胞的消耗会加剧癫痫发作的严重程度和兴奋性毒性诱导的神经元变性,这表明小胶质细胞对兴奋/抑制稳态的变化迅速做出反应,并参与保护神经元免受过度兴奋。
更新日期:2020-08-20
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