Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy  

作　　者：Junzi Chen Yu Wang Cong Chen Qingyang Zhang Shuang Wang Yi Wang Jiajia Fang Ying Wang 

机构地区：[1]Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,School of Pharmaceutical Science,The First Affiliated Hospital,Zhejiang Chinese Medical University,Hangzhou,Zhejiang Province,China [2]Epilepsy Center,The Second Affiliated Hospital,Zhejiang University,Hangzhou,Zhejiang Province,China [3]Department of Neurology,The Fourth Affiliated Hospital,Zhejiang University,Yiwu,Zhejiang Province,China [4]Institute of Neuropsychiatric Diseases,Qingdao University,Qingdao,Shandong Province,China

出　　处：《Neural Regeneration Research》2023年第11期2459-2465,共7页中国神经再生研究（英文版）

基　　金：National Natural Science Foundation of China,Nos.82003 729 (to Ying W),82022071 (to YiW);Natural Science Foundation of Shandong Province of China,No.ZR2020QH357 (to Ying W);Public Welfare Technology Research Program of Zhejiang Province,No.LGF20H09001 1 (to JF)。

摘　　要：Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

关 键 词：ACETYLCHOLINE cholinergic neuron cognitive deficit diffusion tensor imaging hippocampal sclerosis HIPPOCAMPUS medial septum MICRODIALYSIS OPTOGENETICS temporal lobe epilepsy 

分 类 号：R742.1[医药卫生—神经病学与精神病学]