Yang Yong, Zhu Binglin, Zheng Fangshuo, Li Yun, Zhang Yanke, Hu Yida, Wang Xuefeng
Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100101, China.
Biochem Biophys Res Commun. 2017 Mar 4;484(2):450-455. doi: 10.1016/j.bbrc.2017.01.157. Epub 2017 Jan 28.
The AMP-activated protein kinase (AMPK) is a key energy sensor. Its activator metformin could suppress epileptogenesis in the pentylenetetrazol (PTZ) kindling model. However, the effect of metformin on the acute and chronic seizures has not been studied. We first detected the expression of AMPK in the brain tissue of human and mice with chronic seizures, as well as in mice with acute seizures. Second, using behavioral assay and local filed potentials (LFPs) recording, we investigated the effect of chronic metformin treatment on seizures in a acute seizure model and a chronic seizure model. Our results showed that AMPK was expressed in neurons in the epileptic brain. The expression level was decreased in the brain tissue that experienced chronic and acute seizures. In PTZ-induced acute seizures model, behavioral assay showed that chronic metformin treatment decreased the mortality, and LFPs recording showed that chronic metformin treatment shortened the duration of generalized tonic-clonic seizures and prolonged the duration of postictal depression. Moreover, in kainic acid-induced chronic seizures model, LFPs recording showed that chronic metformin treatment shortened the duration of epileptic activity. Our study suggests that chronic metformin treatment could facilitate seizure termination.
AMP激活的蛋白激酶（AMPK）是一种关键的能量传感器。其激活剂二甲双胍可在戊四氮（PTZ）点燃模型中抑制癫痫发生。然而，二甲双胍对急性和慢性癫痫发作的影响尚未得到研究。我们首先检测了慢性癫痫发作的人和小鼠以及急性癫痫发作小鼠脑组织中AMPK的表达。其次，通过行为学检测和局部场电位（LFP）记录，我们研究了慢性二甲双胍治疗对急性癫痫模型和慢性癫痫模型中癫痫发作的影响。我们的结果表明，AMPK在癫痫脑的神经元中表达。在经历慢性和急性癫痫发作的脑组织中，其表达水平降低。在PTZ诱导的急性癫痫发作模型中，行为学检测表明慢性二甲双胍治疗降低了死亡率，LFP记录表明慢性二甲双胍治疗缩短了全身强直阵挛性癫痫发作的持续时间，并延长了发作后抑郁的持续时间。此外，在 kainic 酸诱导的慢性癫痫发作模型中，LFP记录表明慢性二甲双胍治疗缩短了癫痫活动的持续时间。我们的研究表明，慢性二甲双胍治疗可促进癫痫发作的终止。
