Astrocyte–neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury

• DOI: 10.1038/s12276-024-01355-3
• Publication Date: 2024-12-02T01:01:42Z
• Authors: Qing Hu; Xun Wu; Chengxuan Guo; Tinghao Wang; Hao Guo; Jin Wang; Bodong Wang; Wenxing Cui; Hao Bai; Jinpeng Zhou; Leiyang Li; Liying Han; Liang Cao; Shunnan Ge; Guodong Gao; Ting Wang; Zhenyong Wu; Wei Guo; Yan Qu; Jing Feng; Haixiao Liu
• Keywords: Crosstalk; Brain damage; Extracellular vesicles

Abstract Although astrocytes undergo functional changes in response to brain injury and may be the driving force of subsequent neuronal death, underlying mechanisms remain incompletely elucidated. Here, we showed that extracellular vesicle (EV)-shuttled miRNA-382-5p serve as a biomarker for severity traumatic (TBI), circulating EV-miRNA-382-5p level was significantly increased both human patients TBI model mice. Mechanistically, astrocyte-derived EVs delivered shuttled mediate astrocyte–neuron communication, which promoted mitochondrial dysfunction by inhibiting expression optic atrophy-1 (OPA1). Consistent with these findings, genetic ablation OPA1 exacerbated damage apoptosis TBI. Moreover, engineered RVG-miRNA-382-5p inhibitor-EVs, can selectively deliver inhibitor neurons, attenuated improved neurological function after Taken together, our data suggest EV-shuttled critical mediator astrocyte-induced neurotoxicity under pathological conditions targeting miRNA-382-5p-OPA1 signaling has potential clinical translation treatment injury.