Shafia Sakineh, Vafaei Abbas Ali, Samaei Seyed Afshin, Bandegi Ahmad Reza, Rafiei Alireza, Valadan Reza, Hosseini-Khah Zahra, Mohammadkhani Raziyeh, Rashidy-Pour Ali
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Department of Neurology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Neurobiol Learn Mem. 2017 Mar;139:165-178. doi: 10.1016/j.nlm.2017.01.009. Epub 2017 Jan 28.
Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests, the effects of the combined treatment were similar to those of exercise alone, suggesting that exercise is the main factor in the beneficial effects of the combined therapy in PTSD patients.
创伤后应激障碍（PTSD）是个体经历重大创伤后所出现的一种病症。目前，像氟西汀这样的选择性5-羟色胺再摄取抑制剂（SSRIs）是PTSD药物治疗的一线选择，但它们的中等有效率和副作用表明迫切需要研发新的治疗方法。已知体育活动可改善某些神经精神疾病的症状。本研究调查了适度跑步机运动、抗抑郁药氟西汀以及联合治疗对行为缺陷和下丘脑-垂体-肾上腺（HPA）轴功能障碍的影响。我们还在PTSD大鼠模型：单次长时间应激（SPS）模型中检测了海马脑源性神经营养因子（BDNF）的变化以及凋亡相关蛋白的mRNA表达。大鼠接受SPS处理（束缚2小时、强迫游泳20分钟和乙醚麻醉），然后在14天内不进行干扰。之后，对SPS大鼠进行氟西汀慢性治疗（10毫克/千克/天，持续4周）、适度跑步机跑步（4周，每周5天）以及联合治疗（氟西汀加跑步机运动），随后进行行为、生化和凋亡标志物评估。SPS大鼠在高架十字迷宫和明暗箱中表现出焦虑水平升高，在抑制性回避（IA）任务中的恐惧条件反射和消退受损，在识别位置记忆任务中的空间记忆受损，以及在地塞米松抑制试验后HPA轴的负反馈增强。SPS大鼠还表现出海马BDNF减少和凋亡增强。适度跑步机运动、氟西汀和联合治疗在焦虑水平、HPA轴抑制、IA条件反射和消退、海马BDNF和凋亡标志物方面减轻了SPS诱导的改变。此外，联合治疗比单独使用氟西汀更有效，但在大多数测试中，联合治疗的效果与单独运动的效果相似，这表明运动是联合治疗对PTSD患者有益作用的主要因素。
