Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, 127 Changle Road, Xi'an, 710032, Shaanxi, China.
Neurochem Res. 2014 Jan;39(1):172-9. doi: 10.1007/s11064-013-1203-0. Epub 2013 Nov 30.
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.
天麻中的主要成分天麻素(GAS)已被证明可有效治疗各种情绪障碍。本研究旨在评估天麻素对慢性不可预测应激(CUS)大鼠模型中缓解抑郁样行为的影响,并调节来自 Sprague-Dawley(SD)大鼠海马和海马衍生星形胶质细胞中脑源性神经营养因子(BDNF)的表达。在 CUS 后,大鼠每天腹膜内给予天麻素(50、100 或 200mg/kg)或载体 2 周。然后,大鼠经历蔗糖偏好测试和强迫游泳测试。评估海马中 GFAP 和 BDNF 的表达。此外,从新生 SD 大鼠中分离出海马星形胶质细胞,并将其暴露于不同浓度的 GAS(假处理、5、10、20、50 和 100μg/mL)48 和 72 h 后,分析细胞活力以及 pERK1/2 和 BDNF 的水平。此外,还在暴露于含有不同浓度 GAS 的无血清条件下 48 和 72 h 后测试细胞活力。天麻素(100 和 200mg/kg 每天)给药逆转了暴露于 CUS 范式的大鼠的抑郁样行为,并恢复了海马中 GFAP 和 BDNF 的表达。此外,体外实验表明,GAS 不会增加星形胶质细胞的细胞活力,但在剂量为 20μg/mL 时可保护其免受 72 h 无血清损伤。在用 GAS(20μg/mL)处理 72 h 后,还观察到 ERK1/2 磷酸化和 BDNF 蛋白水平升高。星形胶质细胞激活和 BDNF 水平的变化可能在 GAS 的药理作用中起关键作用。