强啡肽
PI3K/AKT/mTOR通路
κ-阿片受体
蛋白激酶B
癫痫发生
海马结构
癫痫
强啡肽A
药理学
化学
类阿片
内分泌学
生物
神经科学
内科学
信号转导
阿片肽
医学
受体
细胞生物学
作者
Hongmei Dai,Peipei Wang,Huafang Mao,Xiao Ou Mao,Shan Tan,Zhiheng Chen
出处
期刊:Cell Cycle
[Informa]
日期:2018-12-30
卷期号:18 (2): 226-237
被引量:27
标识
DOI:10.1080/15384101.2018.1562286
摘要
Dynorphins act as endogenous anticonvulsants via activation of kappa opioid receptor (KOR). However, the mechanism underlying the anticonvulsant role remains elusive. This study aims to investigate whether the potential protection of KOR activation by dynorphin against epilepsy was associated with the regulation of PI3K/Akt/Nrf2/HO-1 pathway. Here, a pilocarpine-induced rat model of epilepsy and Mg2+-free-induced epileptiform hippocampal neurons were established. Decreased prodynorphin (PDYN) expression, suppressed PI3K/Akt pathway, and activated Nrf2/HO-1 pathway were observed in rat epileptiform hippocampal tissues and in vitro neurons. Furthermore, dynorphin activation of KOR alleviated in vitro seizure-like neuron injury via activation of PI3K/Akt/Nrf2/HO-1 pathway. Further in vivo investigation revealed that PDYN overexpression by intra-hippocampus injection of PDYN-overexpressing lentiviruses decreased hippocampal neuronal apoptosis and serum levels of inflammatory cytokines and malondialdehyde (MDA) content, and increased serum superoxide dismutase (SOD) level, in pilocarpine-induced epileptic rats. The protection of PDYN in vivo was associated with the activation of PI3K/Akt/Nrf2/HO-1 pathway. In conclusion, dynorphin activation of KOR protects against epilepsy and seizure-induced brain injury, which is associated with activation of the PI3K/Akt/Nrf2/HO-1 pathway.
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