Nedl1 knockout ameliorates cognitive impairment and improves epilepsy threshold in pilocarpine-induced epileptic mice  

作　　者：Qian Lu Mengjia Liu Shufang Guo Yangyang Wang Liping Zou 

机构地区：[1]Department of Pediatrics,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China [2]Department of Pediatrics,First Hospital of Qinhuangdao,Hebei 066000,China [3]Beijing Children’s Hospital,Capital Medical University,Beijing 100045,China [4]Department of Pediatrics,General Hospital of Air Force,Beijing 100048,China

出　　处：《Acta Epileptologica》2025年第1期68-77,共10页癫痫学报(英文)

基　　金：supported by the National Natural Science Foundation of China(81471329).

摘　　要：Background Epilepsy is a common neurological disorder.The homologous to E6-AP carboxy terminus(HECT)E3 ligase is associated with epilepsy.NEDD4-like ubiquitin protein ligase-1(NEDL1)is a HECT E3 ligase that is highly expressed in the brain.This study aimed to investigate the involvement of NEDL1 in epilepsy and the potential effect of NEDL1 on the cognitive ability.Methods The pilocarpine-induced epileptic mouse model was used to assess cognitive functions in Barnes maze,the pathological changes,and the activation of astrocytes and microglia in wild-type(Nedl1+/+)and Nedl1 knockout(Nedl1−/−)mice.The RNA-seq method was used to analyze differentially expressed genes and explore the brain pathophysiology after epilepsy development.Results Nedl1 knockout resulted in a protective effect against epilepsy.The Nedl1−/−mice showed improved spatial learning and memory,alleviation of pathological damage in the hippocampus induced by epilepsy,and reduced microglial activation in the hippocampus.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes also revealed several prominently enriched T-cell-related pathways.Conclusions Nedl1 knockout reduces seizures and alleviates neuroinflammation.The potential functional link between NEDL1 and epilepsy provides a new approach to the treatment and intervention of epilepsy.

关 键 词：EPILEPSY Cognitive impairment KNOCKOUT Nedl1 

分 类 号：R74[医药卫生—神经病学与精神病学]