Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shangdong, China.
Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shangdong, China.
Neurosci Res. 2020 Aug;157:44-50. doi: 10.1016/j.neures.2019.07.008. Epub 2019 Jul 23.
Hyperphosphorylation of Tau has been found in patients with traumatic brain injury (TBI). Inhibition of c-Jun N-terminal kinases (JNKs) improves neurological function by suppressing Tau phosphorylation. By inhibiting JNK, docosahexaenoic acid (DHA) protects against cognitive decline in a mouse model of Alzheimer's disease (AD). We hypothesize that DHA protects against neuronal damage and behavioral deficits by inhibition of JNK mediated Tau phosphorylation. We induced TBI in mice and examined the phosphorylation status of JNK and Tau. We treated TBI and sham operated mice with DHA, and investigated the effects of DHA on JNK and Tau phosphorylation, hippocampal long term potentiation (LTP), learning and memory, and motor function by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. We found that TBI induction lead to increased phosphorylation of JNK and Tau. DHA suppressed TBI induced JNK and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction, and improved motor function. Inhibition of JNK and Tau phosphorylation by DHA may represent a potential therapeutic strategy for TBI induced neurological dysfunction and Tauopathy.
tau 蛋白过度磷酸化已在创伤性脑损伤（TBI）患者中被发现。抑制 c-Jun N-末端激酶（JNK）可通过抑制 tau 磷酸化来改善神经功能。通过抑制 JNK，二十二碳六烯酸（DHA）可防止阿尔茨海默病（AD）小鼠模型中的认知能力下降。我们假设 DHA 通过抑制 JNK 介导的 tau 磷酸化来防止神经元损伤和行为缺陷。我们在小鼠中诱导 TBI，并检查 JNK 和 tau 的磷酸化状态。我们用 DHA 治疗 TBI 和假手术操作的小鼠，并通过 Western blot 分析、电生理记录和行为评估（包括 Morris 水迷宫测试、平衡木测试、走平衡木测试和转棒测试）来研究 DHA 对 JNK 和 tau 磷酸化、海马长时程增强（LTP）、学习和记忆以及运动功能的影响。我们发现 TBI 诱导导致 JNK 和 tau 磷酸化增加。DHA 抑制 TBI 诱导的 JNK 和 tau 过度磷酸化，挽救 TBI 介导的海马 LTP 缺陷和海马依赖的学习和记忆功能障碍，并改善运动功能。DHA 通过抑制 JNK 和 tau 磷酸化可能代表 TBI 诱导的神经功能障碍和 tau 病的潜在治疗策略。
