Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri.

Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri.
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DOI:
10.4306/pi.2017.14.1.74
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发表时间:
2017-01
影响因子:
2.7
通讯作者:
Mondal AC
Mondal AC
中科院分区:
医学4区
文献类型:
--
作者:
Hazra S;Kumar S;Saha GK;Mondal AC

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本研究旨在探讨假马齿苋提取物(Bacopa monnieri extract,BME)对慢性不可预知应激(chronic unpredictable stress,CUS)所致抑郁模型大鼠行为学的影响,以及对海马脑源性神经营养因子(brain derived neurotrophic factor,BDNF)、Akt、环磷酸腺苷反应元件结合蛋白(cyclic-AMP response element binding,CREB)等生化指标的影响。我们研究了慢性给药BME对CUS暴露大鼠28天的影响。通过蔗糖消耗量和旷场试验评估行为变化,以评估BME对糖尿病诱导的抑郁症的影响。通过测量大鼠脑海马中BDNF、Akt和CREB的水平并与标准三环类抗抑郁药丙咪嗪(20 mg/kg体重)进行比较,进一步评价BME的抗抑郁样作用的潜在机制。暴露于CUS 28天在大鼠中产生抑郁样行为,如通过蔗糖消耗、自发活动(包括海马中BDNF、Akt和CREB水平降低)的显著减少所示。与溶剂处理的对照大鼠相比,每日给予BME(80 mg/kg体重)显著逆转了行为改变,并恢复了CUS诱导大鼠海马中BDNF、总Akt和磷酸化Akt、总CREB和磷酸化CREB的正常水平。这些发现表明,BME改善CUS诱导的大鼠行为抑郁症,并可用作治疗抑郁样行为的有效治疗剂。
The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.