中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (on line): 1-7.

• •    下一篇

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

  

  • 出版日期:2023-01-01 发布日期:2023-03-03

Junzi Chen1, #, Yu Wang1, #, Cong Chen2, #, Qingyang Zhang1, Shuang Wang2, Yi Wang1, 3, *, Jiajia Fang3, *, Ying Wang1, 4, *   

  1. 1Key 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; 2Epilepsy Center, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China; 3Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University, Yiwu, Zhejiang Province, China; 4Institute of Neuropsychiatric Diseases, Qingdao University, Qingdao, Shandong Province, China
  • Online:2023-01-01 Published:2023-03-03
  • Contact: Ying Wang, PhD, wangying@qdu.edu.cn; Jiajia Fang, MD, fangjiajia6926@163.com; Yi Wang, wang-yi@zju.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82003729 (to YingW), 82022071 (to YiW); the Natural Science Foundation of Shandong Province of China, No. ZR2020QH357 (to YingW); and Public Welfare Technology Research Program of Zhejiang Province, No. LGF20H090011 (to JJF).

摘要: https://orcid.org/0000-0003-4616-031X (Ying Wang); 0000-0002-8549-8009 (Jiajia Fang); 0000-0002-1350-2961 (Yi Wang)

Abstract: Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal sclerosis. 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 temporal lobe epilepsy. However, their role in the cognitive impairment of temporal lobe epilepsy remains unclear. In this study, we found that patients with temporal lobe epilepsy 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 tracts measured by diffusion tensor imaging. In a mouse model of chronic temporal lobe epilepsy induced by kainic acid, the number of medial septum cholinergic 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 epilepsy models. These results suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Key words: acetylcholine, cholinergic neuron, cognitive deficit, diffusion tensor imaging, hippocampal sclerosis, hippocampus, medial septum, microdialysis, optogenetics, temporal lobe epilepsy