Pietá Dias C, Martins de Lima M N, Presti-Torres J, Dornelles A, Garcia V A, Siciliani Scalco F, Rewsaat Guimarães M, Constantino L, Budni P, Dal-Pizzol Felipe, Schröder N
Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
Neuroscience. 2007 Jun 8;146(4):1719-25. doi: 10.1016/j.neuroscience.2007.03.018. Epub 2007 Apr 19.
Many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD), are caused by different mechanisms but may share a common pathway to neuronal injury as a result of the overstimulation of glutamate receptors. It has been suggested that this pathway can be involved in generation of cognitive deficits associated with normal aging. Previous studies performed in our laboratory have demonstrated that aged rats presented recognition memory deficits. The aim of the present study was to evaluate the effect of memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, on age-induced recognition memory deficits. Additionally, parameters of oxidative damage in cerebral regions related to memory formation were evaluated. In order to do that, male Wistar rats (24 months old) received daily injections of saline solution or memantine (20 mg/kg i.p.) during 21 days. The animals were submitted to a novel object recognition task 1 week after the last injection. Memantine-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that memantine is able to reverse age-induced recognition memory deficits. We also demonstrated that memantine reduced the oxidative damage to proteins in cortex and hippocampus, two important brain regions involved in memory formation. Thus, the present findings suggest that, at least in part, age-induced cognitive deficits are related to oxidative damage promoted by NMDA receptor overactivation.
许多神经退行性疾病，包括阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD），是由不同机制引起的，但由于谷氨酸受体过度刺激，可能存在共同的神经元损伤途径。有人提出，这一途径可能参与与正常衰老相关的认知缺陷的产生。我们实验室之前进行的研究表明，老年大鼠存在识别记忆缺陷。本研究的目的是评估美金刚（一种低亲和力N-甲基-D-天冬氨酸（NMDA）受体拮抗剂）对年龄诱导的识别记忆缺陷的影响。此外，还评估了与记忆形成相关的脑区氧化损伤参数。为此，雄性Wistar大鼠（24月龄）在21天内每天注射生理盐水或美金刚（20mg/kg，腹腔注射）。在最后一次注射1周后，对动物进行新物体识别任务测试。美金刚治疗组大鼠表现出正常的识别记忆，而生理盐水组表现出长期识别记忆缺陷。结果表明，美金刚能够逆转年龄诱导的识别记忆缺陷。我们还证明，美金刚减少了皮质和海马体（参与记忆形成的两个重要脑区）中蛋白质的氧化损伤。因此，目前的研究结果表明，年龄诱导的认知缺陷至少部分与NMDA受体过度激活促进的氧化损伤有关。
