Gastrodin Ameliorates Depressive-Like Behaviors and Up-Regulates the Expression of BDNF in the Hippocampus and Hippocampal-Derived Astrocyte of Rats
Gastrodin Ameliorates Depressive-Like Behaviors and Up-Regulates the Expression of BDNF in the Hippocampus and Hippocampal-Derived Astrocyte of Rats
复制标题
天麻素改善大鼠海马和海马源性星形胶质细胞的抑郁样行为并上调 BDNF 的表达
DOI：
10.1007/s11064-013-1203-0
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发表时间：
2014-01-01
影响因子：
4.4
通讯作者：
Tan, Qingrong
中科院分区：
文献类型：
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作者：
Zhang, Ruiguo;Peng, Zhengwu;Tan, Qingrong
天麻素（GAS）是中药天麻的主要成分，已被证明可有效治疗各种情绪障碍。本研究的目的是评估GAS对慢性不可预测应激（CUS）大鼠模型抑郁样行为的缓解作用以及对SD大鼠海马和海马源性星形胶质细胞BDNF表达的调节作用。在CUS之后，腹膜内给予大鼠天麻素（每天50、100或200 mg/kg）或媒介物2周。然后进行蔗糖偏好实验和强迫游泳实验。检测海马GFAP和BDNF的表达。另外，分离新生SD大鼠海马星形胶质细胞，用不同浓度的GAS（sham、5、10、20、50和100 μg/mL）处理48和72 h，然后分析细胞活力、pERK 1/2和BDNF水平。此外，还在暴露于含有不同浓度GAS的无血清条件48和72 h后检测细胞活力。GAS给药（100和200 mg/kg/d）可逆转CUS模型大鼠的抑郁样行为，并恢复海马GFAP和BDNF的表达。体外实验表明，GAS在20 μg/mL浓度下对星形胶质细胞无血清培养72 h后的细胞存活率无明显影响，但对星形胶质细胞无血清培养72 h后的细胞存活率无明显影响。GAS（20 μg/mL）处理72 h后，ERK 1/2磷酸化水平和BDNF蛋白表达水平均明显升高。提示天麻素具有抗抑郁作用。星形胶质细胞活化和脑源性神经营养因子水平的变化可能在GAS的药理作用中发挥关键作用。
Gastrodin (GAS), a main constituent of a Chinese herbal medicine Tian ma, has been shown to be effective in treating various mood disorders. The purpose of the present study was to assess the effects of GAS on alleviating depressive-like behaviors in a rat model of chronic unpredictable stress (CUS) and regulating the expression of BDNF in the hippocampus and hippocampal-derived astrocyte from Sprague–Dawley (SD) rats. Following CUS, rats were intraperitoneally administered gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Rats were then experienced sucrose preference test and forced swim test. The expressions of GFAP and BDNF in the hippocampus were evaluated. In addition, hippocampal astrocytes were isolated from neonatal SD rats and exposed to different concentrations of GAS (sham, 5, 10, 20, 50 and 100 μg/mL) for 48 and 72 h before the cell viability and the levels of pERK1/2 and BDNF were analyzed. Furthermore, the cell viability was also tested after exposure to serum-free condition that contain different concentrations of GAS for 48 and 72 h. GAS administration (100 and 200 mg/kg daily) reversed depressive-like behaviors in rats exposed to CUS paradigm and restored the expression of GFAP and BDNF in the hippocampus. Moreover, in vitro experiments revealed that GAS did not increase the cell viability of astrocytes but protected it from 72 h’s serum-free damage at the dosage 20 μg/mL. Increased levels of ERK1/2 phosphorylation and BDNF protein were also observed after GAS (20 μg/mL) treatment for 72 h. These results indicate that gastrodin possesses antidepressant effect. The changes of the astrocyte activation and the level of BDNF may play a critical role in the pharmacological action of GAS.