Raghavendra V, Kulkarni S K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Free Radic Biol Med. 2001 Mar 15;30(6):595-602. doi: 10.1016/s0891-5849(00)00447-0.
Cognitive dysfunction is one of the most striking age-related impairments seen in human beings and animals. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Pineal hormone melatonin is reported to be an endogenous antioxidant, whose peak plasma level declines during aging and in Alzheimer's disease (AD). Present experiments were performed to study the possible effect of exogenously administered melatonin on cognitive performance of young, aged, or ethanol-intoxicated mice (an animal model for AD) using one trial step-down type of passive avoidance and elevated plus-maze task. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of melatonin (0.1-10 mg/kg, sc) for 30 d or its coadministration with ethanol (15% W/V, 2 g/kg perorally) for 24 d significantly reversed the age-induced or chronic ethanol-induced retention deficits in both the test paradigms. However, in both the memory paradigms chronic administration of melatonin failed to modulate the retention performance of young mice. Chronic administration of melatonin (0.1-10 mg/kg) for 30 d also reversed age-associated decline in forebrain total glutathione (tGSH) level. Chronic ethanol administration to young mice produced decline in forebrain tGSH level and enhanced brain lipid peroxidation, which was significantly reversed by coadministration of melatonin (10 mg/kg). The results of this study showed chronic melatonin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.
认知功能障碍是人类和动物中最显著的与年龄相关的损伤之一。这种损伤可能是由于衰老过程中脑细胞对氧化应激增加的易感性所致。据报道，松果体激素褪黑素是一种内源性抗氧化剂，其血浆峰值水平在衰老和阿尔茨海默病（AD）期间会下降。本实验采用一步式被动回避和高架十字迷宫任务，研究外源性给予褪黑素对年轻、老年或乙醇中毒小鼠（AD动物模型）认知能力的可能影响。老年或慢性乙醇处理的小鼠在被动回避和高架十字迷宫任务中的记忆保持能力较差。连续30天给予褪黑素（0.1 - 10 mg/kg，皮下注射）或与乙醇（15% W/V，2 g/kg口服）共同给药24天，在两种测试范式中均显著逆转了年龄诱导或慢性乙醇诱导的记忆保持缺陷。然而，在两种记忆范式中，连续给予褪黑素未能调节年轻小鼠的记忆保持表现。连续30天给予褪黑素（0.1 - 10 mg/kg）也逆转了与年龄相关的前脑总谷胱甘肽（tGSH）水平下降。对年轻小鼠慢性给予乙醇会导致前脑tGSH水平下降并增强脑脂质过氧化，而褪黑素（10 mg/kg）共同给药可显著逆转这一现象。本研究结果表明，慢性褪黑素治疗可逆转老年和乙醇中毒小鼠的认知缺陷，这与其抗氧化特性有关。
