Mokhtari Zahra, Baluchnejadmojarad Tourandokht, Nikbakht Farnaz, Mansouri Monireh, Roghani Mehrdad
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Biomed Pharmacother. 2017 Mar;87:135-144. doi: 10.1016/j.biopha.2016.12.067. Epub 2016 Dec 31.
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists. Further biochemical analysis showed that riluzole pretreatment of intrahippocampal Aβ-microinjected rats is able to attenuate hippocampal AChE activity and lower some oxidative stress markers, i.e. MDA and nitrite, with no significant change of the defensive enzyme catalase. Furthermore, riluzole prevented hippocampal CA1 neuronal loss and reduced 3-nitrotyrosine immunoreactivity. It is concluded that riluzole could exert a protective effect against memory decline induced by intrahippocampal Aβ through anti-oxidative, anti-cholinesterase, and neuroprotective potential and its beneficial effect is possibly independent of cholinoceptor activation.
阿尔茨海默病（AD）是一个重大的全球公共卫生问题和社会护理问题，与学习、记忆和认知缺陷相关。利鲁唑是一种谷氨酸调节剂，已显示可改善老年大鼠的记忆表现，可能对阿尔茨海默病有益。在本研究中，评估了其对Aβ诱导的AD大鼠模型学习和记忆缺陷的减轻作用。以10mg/kg/天的剂量口服给予利鲁唑可改善莫里斯水迷宫中的空间记忆以及被动回避任务中的记忆保持和回忆，并且在脑室内微量注射毒蕈碱或烟碱受体拮抗剂后其保护作用未被中和。进一步的生化分析表明，对海马内注射Aβ的大鼠进行利鲁唑预处理能够减弱海马乙酰胆碱酯酶活性并降低一些氧化应激标志物，即丙二醛和亚硝酸盐，而防御酶过氧化氢酶无明显变化。此外，利鲁唑可防止海马CA1神经元丢失并降低3-硝基酪氨酸免疫反应性。得出的结论是，利鲁唑可通过抗氧化、抗胆碱酯酶和神经保护作用对海马内Aβ诱导的记忆衰退发挥保护作用，并且其有益作用可能独立于胆碱受体激活。
