Li Fu, Xiang Haitao, Lu Jiashu, Chen Zhuo, Huang Chao, Yuan Xiaomei
Department of Pharmacy, The Seventh People's Hospital of Changzhou, 288# Yanling East Road, Changzhou 213000, Jiangsu, China.
Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, #118 Wansheng Street, Suzhou 215028, Jiangsu, China.
Physiol Behav. 2020 Oct 1;224:113026. doi: 10.1016/j.physbeh.2020.113026. Epub 2020 Jun 24.
Posttraumatic stress disorder (PTSD) is a mental disorder that can translate into severe economic problems. Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants, including papayas, tomatoes, and water melons. Previous studies have shown that lycopene can produce antidepressant-like effects in rodent models of depression. However, little is known about its anti-PTSD-like effect. This was addressed in the present study by using the single prolonged stress (SPS) protocol to induce PTSD-like behavioral deficits in mice. Our results showed that 12 days of lycopene treatment at the dose of 10 and 20 mg/kg, but not at 5 mg/kg, ameliorated the PTSD-like phenotype induced by SPS, including the increase in freezing time in contextual fear paradigm, the decrease in time and entries in open arms in elevated plus maze test, and the decrease in distance and time in the central area of the open field test, without affecting the mouse locomotor activity. Mechanistic studies revealed that lycopene treatment (20 mg/kg, 12 days) could suppress the SPS-induced increase in levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and nitrite in the hippocampus and prefrontal cortex in mice, as well as the increased markers that indicate high levels of oxido-nitrosative stress in the hippocampus and prefrontal cortex in SPS mice. Lycopene treatment (20 mg/kg, 12 days) also suppressed the SPS-induced decrease in brain derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex in mice. Overall, the anti-PTSD-like effect of lycopene may be associated with its anti-neuroinflammation and anti-oxidative stress activities.
创伤后应激障碍（PTSD）是一种可能转化为严重经济问题的精神障碍。番茄红素是一种从植物中提取的脂肪烃类胡萝卜素，这些植物包括木瓜、番茄和西瓜。先前的研究表明，番茄红素在抑郁症啮齿动物模型中可产生抗抑郁样作用。然而，关于其抗创伤后应激障碍样作用却知之甚少。本研究通过使用单次长时间应激（SPS）方案在小鼠中诱导创伤后应激障碍样行为缺陷来解决这一问题。我们的结果表明，以10和20 mg/kg剂量但非5 mg/kg剂量的番茄红素处理12天，可改善由SPS诱导的创伤后应激障碍样表型，包括情境恐惧范式中僵住时间的增加、高架十字迷宫试验中进入开放臂的时间和次数的减少以及旷场试验中央区域的距离和时间的减少，且不影响小鼠的运动活动。机制研究表明，番茄红素处理（20 mg/kg，12天）可抑制SPS诱导的小鼠海马体和前额叶皮质中白细胞介素-6（IL-6）、IL-1β、肿瘤坏死因子-α（TNF-α）和亚硝酸盐水平的升高，以及SPS小鼠海马体和前额叶皮质中表明氧化亚硝化应激水平升高的标志物的增加。番茄红素处理（20 mg/kg，12天）还抑制了SPS诱导的小鼠海马体和前额叶皮质中脑源性神经营养因子（BDNF）水平的降低。总体而言，番茄红素的抗创伤后应激障碍样作用可能与其抗神经炎症和抗氧化应激活性有关。
