Lee Bombi, Shim Insop, Lee Hyejung, Hahm Dae-Hyun
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
Center for Converging Humanities, Kyung Hee University, Seoul, 02447, Republic of Korea.
BMC Neurosci. 2018 Jul 4;19(1):38. doi: 10.1186/s12868-018-0439-7.
Post-traumatic stress disorder (PTSD) is an important psychological disease that can develop following the physical experience or witnessing of traumatic events. The psychopathological response to traumatic stressors increases inflammation in the hippocampus and induces memory deficits. Melatonin (MTG) plays critical roles in circadian rhythm disorders, Alzheimer's disease, and other neurological disorders. However, the cognitive efficiency of MTG and its mechanisms of action in the treatment of PTSD remain unclear. Thus, the present study investigated the effects of MTG on spatial cognitive impairments stimulated by single prolonged stress (SPS) in rats, an animal model of PTSD. Male rats received intraperitoneal (i.p.) administration of various doses of MTG for 21 consecutive days after the SPS procedure.
SPS-stimulated cognitive impairments in the object recognition task and Morris water maze were reversed by MTG treatment (25 mg/kg, i.p). Additionally, MTG significantly increased cognitive memory-related decreases in cAMP-response element-binding (CREB) protein and mRNA levels in the hippocampus. Our results also demonstrate that MTG significantly inhibited SPS-stimulated cognitive memory impairments by inhibiting the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the rat brain.
The present results indicate that MTG can be beneficial for SPS-stimulated memory impairments via changes in CREB expression and proinflammatory mediators. Thus, MTG may be a prophylactic strategy for the prevention or mitigation of the progression of some features of the PTSD pathology.
创伤后应激障碍（PTSD）是一种重要的心理疾病，可在经历创伤事件或目睹创伤事件后发生。对创伤应激源的心理病理反应会增加海马体中的炎症并导致记忆缺陷。褪黑素（MTG）在昼夜节律紊乱、阿尔茨海默病和其他神经疾病中起关键作用。然而，MTG的认知效率及其在PTSD治疗中的作用机制仍不清楚。因此，本研究调查了MTG对创伤后应激障碍动物模型大鼠中由单次长时间应激（SPS）刺激引起的空间认知障碍的影响。雄性大鼠在SPS程序后连续21天腹腔注射（i.p.）不同剂量的MTG。
MTG治疗（25mg/kg，腹腔注射）可逆转SPS刺激在物体识别任务和莫里斯水迷宫中的认知障碍。此外，MTG显著增加了海马体中与认知记忆相关的环磷酸腺苷反应元件结合蛋白（CREB）蛋白和mRNA水平的降低。我们的结果还表明，MTG通过抑制大鼠脑中促炎细胞因子的表达，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），显著抑制了SPS刺激的认知记忆障碍。
目前的结果表明，MTG可通过CREB表达和促炎介质的变化对SPS刺激的记忆障碍有益。因此，MTG可能是预防或减轻PTSD病理某些特征进展的一种预防策略。
