Du Yuan, Liang Haiyue, Zhang Leiming, Fu Fenghua
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, PR China.
Yantai Center for Food and Drug Control, Yantai 264000, PR China.
Pharmacol Biochem Behav. 2017 Jul;158:32-38. doi: 10.1016/j.pbb.2017.06.002. Epub 2017 Jun 3.
Post-stroke depression (PSD) is the most common mood disorder following a stroke, and is also the main factor limiting recovery and rehabilitation in stroke patients. The present study was aimed to investigate whether Huperzine A (HupA) has antidepressant-like activity in a rat model of PSD, which was developed by middle cerebral artery occlusion followed by an 18-day chronic unpredictable mild stress in conjunction with isolation rearing. The sucrose preference and forced swim tests were used to assess depression-like behavior. Neurological and cognitive functions following ischemia were evaluated by neurological evaluation, the beam-walking test, the forelimb grip force test, and the water maze test. Levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hippocampus and prefrontal cortex were assayed by high performance liquid chromatography. Western blot analysis was used to evaluate hippocampal expression of the 5-hydroxytryptamine 1A receptor (5-HTR), cAMP response element binding (CREB), phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF). The results showed that treatment with HupA for 4weeks ameliorated behavioral abnormalities and the impairment of neurological and cognitive functions in PSD rats. This was accompanied by the upregulated hippocampal expression of 5-HTR, p-CREB and BDNF, and increased levels of NE, DA, and 5-HT in the hippocampus and prefrontal cortex. These findings suggest that HupA has antidepressant-like effect and can improve neurological and cognitive functions in PSD rats, which suggest its therapeutic potential for depression after stroke.
中风后抑郁症（PSD）是中风后最常见的情绪障碍，也是限制中风患者恢复和康复的主要因素。本研究旨在调查石杉碱甲（HupA）在PSD大鼠模型中是否具有抗抑郁样活性，该模型通过大脑中动脉闭塞，随后进行18天的慢性不可预测轻度应激并结合隔离饲养建立。采用蔗糖偏好试验和强迫游泳试验评估抑郁样行为。通过神经学评估、横梁行走试验、前肢握力试验和水迷宫试验评估缺血后的神经和认知功能。采用高效液相色谱法测定海马和前额叶皮质中去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）的水平。蛋白质免疫印迹分析用于评估海马中5-羟色胺1A受体（5-HTR）、cAMP反应元件结合蛋白（CREB）、磷酸化CREB（p-CREB）和脑源性神经营养因子（BDNF）的表达。结果表明，用HupA治疗4周可改善PSD大鼠的行为异常以及神经和认知功能障碍。这伴随着海马中5-HTR、p-CREB和BDNF表达上调，以及海马和前额叶皮质中NE、DA和5-HT水平升高。这些发现表明，HupA具有抗抑郁样作用，可改善PSD大鼠的神经和认知功能，提示其对中风后抑郁症的治疗潜力。
