Zhao Li, Zhang Lei, Zhu Wei, Chen Hongguang, Ding Yuexia, Cui Guangqiang
Department of Pharmacy, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai 264000, Shangdong, China.
Department of Neurosurgery, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai 264000, Shangdong, China.
Physiol Behav. 2021 Jan 1;228:113190. doi: 10.1016/j.physbeh.2020.113190. Epub 2020 Sep 28.
Traumatic brain injury (TBI) can lead to cognitive dysfunction and motor dysfunction. TBI is a potential risk factor for subsequent dementia. Hyperphosphorylation of Tau and ApoE4 has been found in patients with TBI. A significant increase in miR-203 was also found in the peripheral blood of TBI mice. Thus, we hypothesize that miR-203 inhibitor protects against neuronal damage and behavioral deficits by inhibition of Tau phosphorylation, ApoE4 expression and apoptosis.
TBI mice were induced and treated with miR-203 inhibitor. Tau phosphorylation and ApoE4, hippocampal long-term potentiation (LTP), learning and memory, and motor function were separately detected by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. Caspase-3 activity and bcl-2 expression were detected by ELISA.
TBI induction led to increased phosphorylation of Tau and ApoE4 expression. Administration of miR-203 inhibitor suppressed TBI induced ApoE4 expression and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction. miR-203 inhibitor treatment also improved motor function. In addition, miR-203 inhibitor treatment inhibited neuronal apoptosis by inhibiting caspase-3 activity and increasing bcl-2 expression.
miR-203 inhibitor treatment can rescue TBI-induced neural damage by inhibiting neuronal apoptosis and dementia markers like ApoE4 expression and Tau phosphorylation.
创伤性脑损伤（TBI）可导致认知功能障碍和运动功能障碍。TBI是后续发生痴呆的一个潜在风险因素。在TBI患者中已发现Tau蛋白过度磷酸化和载脂蛋白E4（ApoE4）。在TBI小鼠的外周血中也发现miR-203显著增加。因此，我们推测miR-203抑制剂可通过抑制Tau磷酸化、ApoE4表达和细胞凋亡来预防神经元损伤和行为缺陷。
诱导TBI小鼠并给予miR-203抑制剂治疗。通过蛋白质免疫印迹分析、电生理记录以及包括莫里斯水迷宫试验、横梁平衡试验、横梁行走试验和转棒试验在内的行为评估分别检测Tau磷酸化和ApoE4、海马长时程增强（LTP）、学习和记忆以及运动功能。通过酶联免疫吸附测定法检测半胱天冬酶-3（Caspase-3）活性和bcl-2表达。
诱导TBI导致Tau磷酸化增加和ApoE4表达增加。给予miR-203抑制剂可抑制TBI诱导的ApoE4表达和Tau过度磷酸化，挽救TBI介导的海马LTP缺陷以及海马依赖性学习和记忆功能障碍。miR-203抑制剂治疗还改善了运动功能。此外，miR-203抑制剂治疗通过抑制Caspase-3活性和增加bcl-2表达来抑制神经元凋亡。
miR-203抑制剂治疗可通过抑制神经元凋亡以及ApoE4表达和Tau磷酸化等痴呆标志物来挽救TBI诱导的神经损伤。
