Lu Cui Yan, Liu De Xiang, Jiang Hong, Pan Fang, Ho Cyrus S H, Ho Roger C M
Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
Department of Psychological Medicine, National University of Singapore, Singapore 119228.
Neural Plast. 2017;2017:5715816. doi: 10.1155/2017/5715816. Epub 2017 Mar 2.
Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD). Gamma-aminobutyric acid (GABA) deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAR) subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAR subunits (2, 2, and 5) in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam) for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.
研究发现，早期创伤经历会显著增加创伤后应激障碍（PTSD）的风险。有人提出γ-氨基丁酸（GABA）缺乏与PTSD的发生有关，但早期创伤应激诱导的GABA A受体（GABAR）亚基的改变尚未完全阐明。此外，先前的研究表明，运动在减轻焦虑和抑郁严重程度方面可能比药物更有效，但其机制尚不清楚。本研究采用不可逃避的足部电击在幼年大鼠中诱导PTSD，并使用旷场试验和高架十字迷宫检测其情绪变化，使用莫里斯水迷宫检测记忆变化，使用蛋白质免疫印迹法和免疫组织化学检测成年大鼠大脑各亚区GABAR亚基（α2、β2和γ5）的表达。我们旨在观察幼年创伤诱导的GABAR亚基变化在成年期后续PTSD发病机制中的作用。此外，我们研究了为期6周的运动和为期2周的苯二氮䓬类药物（氯硝西泮）的保护作用。本研究发现，幼年创伤应激会导致成年大鼠慢性焦虑和空间记忆丧失，并降低成年大鼠大脑中GABAR亚基的表达。此外，与短期苯二氮䓬类药物治疗相比，运动导致了显著改善。
