Neuronal small extracellular vesicles carrying miR-181c-5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C-δ/glutamate transporter-1 axis in astrocytes

作者全名:"Ma, Limin; Wu, Qingyuan; You, Yu; Zhang, Peng; Tan, Dandan; Liang, Minxue; Huang, Yunyi; Gao, Yuan; Ban, Yuenan; Chen, Yangmei; Yuan, Jinxian"

作者地址:"[Ma, Limin; You, Yu; Zhang, Peng; Tan, Dandan; Liang, Minxue; Huang, Yunyi; Gao, Yuan; Ban, Yuenan; Chen, Yangmei; Yuan, Jinxian] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Ma, Limin; Wu, Qingyuan] Chongqing Univ, Three Gorges Hosp, Dept Neurol, Chongqing, Peoples R China"

通信作者:"Chen, YM; Yuan, JX (通讯作者),Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, 74 Linjiang Rd, Chongqing 400010, Peoples R China."












关键词:astrocyte; epilepsy; extracellular vesicles; glutamate; miR-181c-5p; seizure

摘要:"Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter-1 (GLT-1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR-181c-5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV-derived miR-181c-5p interacted with protein kinase C-delta (PKC delta), downregulated PKC delta and GLT-1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR-181c-5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy."

基金机构:Natural Science Foundation of Chongqing Municipality

基金资助正文:No Statement Availabler No Statement Available