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Nedl1基因敲除改善了毛果芸香碱诱导的癫痫小鼠的认知障碍并提高了癫痫阈值。

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

作者信息

Lu Qian, Liu Mengjia, Guo Shufang, Wang Yangyang, Zou Liping

机构信息

Department of Pediatrics, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Department of Pediatrics, First Hospital of Qinhuangdao, Hebei, 066000, China.

出版信息

Acta Epileptol. 2025 Jan 13;7(1):5. doi: 10.1186/s42494-024-00186-z.

DOI:10.1186/s42494-024-00186-z
PMID:40217560
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11960318/
Abstract

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.

摘要

背景

癫痫是一种常见的神经系统疾病。E6相关蛋白羧基末端同源物（HECT）E3连接酶与癫痫有关。NEDD4样泛素蛋白连接酶1（NEDL1）是一种在大脑中高度表达的HECT E3连接酶。本研究旨在探讨NEDL1在癫痫中的作用及其对认知能力的潜在影响。

方法

采用毛果芸香碱诱导的癫痫小鼠模型，评估野生型（Nedl1）和Nedl1基因敲除（Nedl1）小鼠在巴恩斯迷宫中的认知功能、病理变化以及星形胶质细胞和小胶质细胞的激活情况。采用RNA测序方法分析差异表达基因，并探讨癫痫发作后大脑的病理生理学变化。

结果

Nedl1基因敲除对癫痫具有保护作用。Nedl1基因敲除小鼠的空间学习和记忆能力得到改善，癫痫诱导的海马病理损伤减轻，海马小胶质细胞激活减少。对差异表达基因的京都基因与基因组百科全书（KEGG）分析还揭示了几个显著富集的T细胞相关途径。

结论

Nedl1基因敲除可减少癫痫发作并减轻神经炎症。NEDL1与癫痫之间潜在的功能联系为癫痫的治疗和干预提供了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/08ea9a85720f/42494_2024_186_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/513ed514b81b/42494_2024_186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/0bcc73c9c52b/42494_2024_186_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/f5801d543ac4/42494_2024_186_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/5ae06c6355bb/42494_2024_186_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/8459d176a223/42494_2024_186_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/08ea9a85720f/42494_2024_186_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/513ed514b81b/42494_2024_186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/0bcc73c9c52b/42494_2024_186_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/f5801d543ac4/42494_2024_186_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/5ae06c6355bb/42494_2024_186_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/8459d176a223/42494_2024_186_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b46/11960318/08ea9a85720f/42494_2024_186_Fig6_HTML.jpg

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