小胶质细胞耗竭加重了小鼠急性和慢性癫痫发作的严重程度。
Microglial depletion aggravates the severity of acute and chronic seizures in mice.
机构信息
Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
出版信息
Brain Behav Immun. 2020 Oct;89:245-255. doi: 10.1016/j.bbi.2020.06.028. Epub 2020 Jul 2.
Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1:R26, CX3CR1:R26, and CX3CR1:Csf1r mice. We found that microglial depletion led to worse kainic acid (KA)-induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy.
小胶质细胞是中枢神经系统的固有免疫细胞，参与多种神经疾病。在这里，我们使用小胶质细胞消融方法来确定小胶质细胞在癫痫发生中的作用。我们使用了三种不同的小胶质细胞特异性基因工具，即 CX3CR1:R26、CX3CR1:R26 和 CX3CR1:Csf1r 小鼠。我们发现小胶质细胞耗竭导致更严重的海人酸（KA）诱导的癫痫持续状态，更高的死亡率，并增加海马中的神经元变性。在 KA 诱导的慢性自发性反复性发作中，小胶质细胞耗竭增加了发作频率、发作间棘波和发作持续时间。因此，小胶质细胞耗竭加重了 KA 诱导的急性和慢性发作的严重程度。有趣的是，小胶质细胞再定植逆转了耗竭对 KA 诱导的癫痫持续状态的影响。我们的结果表明小胶质细胞在抑制急性和慢性发作方面具有有益作用，提示小胶质细胞可能是治疗癫痫的潜在治疗靶点。
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