Ostrovskaya R U, Gudasheva T A, Zaplina A P, Vahitova Ju V, Salimgareeva M H, Jamidanov R S, Seredenin S B
V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.
Bull Exp Biol Med. 2008 Sep;146(3):334-7. doi: 10.1007/s10517-008-0297-x.
We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease.
我们研究了具有促智和神经保护特性的原二肽制剂诺沛(N-苯乙酰基-L-脯氨酰甘氨酸乙酯,GVS-111)对大鼠海马中神经营养因子NGF和BDNF的mRNA表达的影响。通过Northern印迹分析研究了大脑皮层和海马中NGF和BDNF mRNA的表达。考虑到诺沛的药理活性在急性和慢性治疗后均能实现,我们研究了单次和长期(28天)使用该药物的效果。单次给予诺沛后,大脑皮层中所研究的神经营养因子的表达低于对照组,而长期给药则导致BDNF表达略有增加。在海马中,急性给予诺沛后两种神经营养蛋白的mRNA表达均增加。诺沛的长期治疗并未导致耐受性的产生,反而增强了神经营养作用。这些变化可能在神经元修复中起作用。我们表明,促智药物可增加海马中神经营养因子的表达。我们的结果与以下假设一致,即海马中的神经营养因子合成决定认知功能,特别是在巩固和延迟记忆检索方面。已发表的数据表明,不仅在晚期阿尔茨海默病中,而且在轻度认知障碍阶段(疾病前期状态)也观察到海马中的神经营养因子缺乏。鉴于此,我们的研究结果表明,诺沛在预防轻度认知障碍患者发生阿尔茨海默病方面具有很大潜力。此外,应在阿尔茨海默病的初始阶段评估诺沛的治疗效果。