The sigma-1 receptor-TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis  

作　　者：Jianlun Ji Ce Gao Qinghua Wang Xiaoxia Jia Hao Tian Yaqin Wei Zhidong Liu Yun Wang Lin Guo 

机构地区：[1]Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,China [2]Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,China [3]Agro-Products Processing Research Institute,Yunnan Academy of Agricultural Sciences,Kunming,China

出　　处：《Animal Models and Experimental Medicine》2025年第2期197-208,共12页动物模型与实验医学(英文)

基　　金：This project was supported by grants from the National Natural Science Foundation of China(Grant Nos.81872847 and 82173803);the Science and Technology Planning Project of Xuzhou(Grant No.KC22256);the Science and Technology Developing Fund of The Affiliated Hospital of Xuzhou Medical University(Grant No.2021ZA14)。

摘　　要：Background:Therapy in the latent period is favorable for retarding the process of epileptogenesis.Recently,we have discovered that the activated sigma-1 receptor(Sig-1R)attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis.But the molecular mechanism needs further investigation.Methods:PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice.After the treatment of PRE-084,the pro-inflammatory cytokines,neuropathological traits,and the level of mitochondrial translocator assembly and maintenance 41 homolog(TAMM41)in the hippocampus were examined.The mode in which the Sig-1R interacts with TAMM41 was explored.The role of TAMM41 in the protecting effect of PRE-084 was established.Results:PRE-084 inhibited the growth of pro-inflammatory cytokines,reduced the formation of gliosis,alleviated neuronal damage in the hippocampus,and attenu-ated memory impairment in the latent period of epileptogenesis.The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice.The Sig-1R bound with TAMM41 directly,maintaining the stability of TAMM41.Knockdown of TAMM41 reversed the protective effect of PRE-084,and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084.Conclusion:We presented the concept of the“sigma-1 receptor–TAMM41 axis”and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.

关 键 词：EPILEPTOGENESIS memory impairment mitochondrial translocator assembly and maintenance 41 homolog NEUROINFLAMMATION sigma-1 receptor 

分 类 号：R74[医药卫生—神经病学与精神病学]