Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model
Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model
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DOI：
10.1016/j.jep.2017.06.024
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发表时间：
2017-07-31
影响因子：
5.4
通讯作者：
Son, Chang-Gue
中科院分区：
文献类型：
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作者：
Lee, Jin-Seok;Kim, Hyeong-Geug;Son, Chang-Gue
民族药理相关性：赤松叶传统上被用作治疗精神健康障碍的一种传统中药。本研究旨在探讨松针对应激所致记忆障碍的民族药理作用。目的：采用急性束缚应激小鼠模型，探讨30%松针乙醇提取物(PNE)对应激诱导的海马神经元兴奋性毒性的可能调节作用。材料和方法：给小鼠灌胃PNE(25、50、100 mg/kg)或抗坏血酸(100 mg/kg)9天，然后给予束缚应激(6h/d)3天(从实验第7~9天开始)。在实验第5~9天进行Morris水迷宫测试。结果：束缚应激可导致大鼠记忆障碍(逃避潜伏期延长、路径累积长度延长、在目标象限停留时间减少)，PNE治疗可显著阻止这种作用。束缚应激使大鼠血清/海马区皮质酮及其受体水平升高，经去甲肾上腺素处理后皮质酮及其受体水平恢复正常。束缚应激可引起大鼠海马区兴奋性毒性、炎症反应和氧化损伤，表现为谷氨酸水平升高、肿瘤坏死因子-α水平改变和氧化-抗氧化平衡失衡。针对胶质纤维酸性蛋白(GFAP)阳性星形胶质细胞和神经元核(NeUN)阳性神经元的两种免疫组织化学活性支持兴奋性毒性的发现，特别是在海马氨角(CA)3区。给予PNE可显著减轻上述改变。结论：上述结果表明，PNE具有调节严重应激条件下大鼠海马区兴奋性毒性所致记忆损害的药理作用。
Ethnopharmacological relevance: The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress.Aim of the study: To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model.Materials and methods: Mice were orally administered with PNE (25, 50, or 100 mg/kg) or ascorbic acid (100 mg/kg) for 9 days, and were then subjected to restraint stress (6 h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9.Results: Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-alpha and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE.Conclusions: The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions.