Saraf M K, Prabhakar S, Pandhi P, Anand A
Department of Neurology, Neuroscience Research Laboratory, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India.
Neuroscience. 2008 Aug 13;155(2):476-84. doi: 10.1016/j.neuroscience.2008.05.043. Epub 2008 Jun 7.
Benzodiazepines are known to produce amnesia by involvement of GABAergic system and by interference of long term potentiation (LTP). In this study, we examined effect of Bacopa monniera on downstream molecules of LTP after diazepam-induced amnesia in mice. We used a Morris water maze scale for evaluating the effect of Bacopa monniera after screening for muscle coordination by rota rod. The index of acquisition and retrieval was recorded as escape latency time (ELT). Behavioral results showed that Bacopa monniera (120 mg kg(-1) oral) significantly reversed diazepam- (1.75 mg kg(-1) i.p.) induced amnesia in Morris water maze task. The molecular studies revealed that diazepam upregulated mitogen activated protein kinase (MAP kinase), phosphorylated CREB (pCREB) and inducible nitric oxide synthase (iNOS), while it downregulated nitrite, nitrate, total nitrite, cAMP response element binding protein (CREB) expression, phosphodiesterase, cyclic adenosine monophosphate (cAMP) without affecting calmodulin levels. Bacopa monniera suppressed the diazepam induced upregulation of MAP kinase, pCREB and iNOS and attenuated the downregulation of nitrite. It did not affect the cAMP, PDE, nitrate, total nitrite, total CREB level. These behavioral findings displayed the reversal of diazepam-induced amnesia by Bacopa monniera without qualifying the molecular details although some downstream molecules of LTP may be involved.
已知苯二氮䓬类药物通过影响γ-氨基丁酸能系统和干扰长时程增强(LTP)产生失忆作用。在本研究中,我们检测了在小鼠中,水龙骨对安定诱导失忆后LTP下游分子的影响。我们使用Morris水迷宫量表评估水龙骨的效果,此前通过转棒试验筛选了其对肌肉协调性的影响。将获取和检索指标记录为逃避潜伏期(ELT)。行为学结果显示,水龙骨(120 mg kg(-1)口服)显著逆转了安定(1.75 mg kg(-1)腹腔注射)在Morris水迷宫任务中诱导的失忆。分子研究表明,安定上调了丝裂原活化蛋白激酶(MAP激酶)、磷酸化的cAMP反应元件结合蛋白(pCREB)和诱导型一氧化氮合酶(iNOS),同时下调了亚硝酸盐、硝酸盐、总亚硝酸盐、cAMP反应元件结合蛋白(CREB)表达、磷酸二酯酶、环磷酸腺苷(cAMP),而不影响钙调蛋白水平。水龙骨抑制了安定诱导的MAP激酶、pCREB和iNOS的上调,并减弱了亚硝酸盐的下调。它不影响cAMP、磷酸二酯酶、硝酸盐、总亚硝酸盐、总CREB水平。这些行为学发现显示水龙骨可逆转安定诱导的失忆,尽管可能涉及LTP的一些下游分子,但未明确分子细节。