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大鼠与年龄相关的学习和记忆缺陷:脑内神经递质改变、乙酰胆碱酯酶活性及抗氧化防御系统变化的作用

Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

作者信息

Haider Saida, Saleem Sadia, Perveen Tahira, Tabassum Saiqa, Batool Zehra, Sadir Sadia, Liaquat Laraib, Madiha Syeda

机构信息

Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan,

出版信息

Age (Dordr). 2014 Jun;36(3):9653. doi: 10.1007/s11357-014-9653-0. Epub 2014 Apr 27.

Abstract

Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

摘要

据报道,活性氧或氧自由基生成增加所导致的氧化应激在衰老过程中起重要作用。为了研究衰老过程中氧化应激与记忆衰退之间的关系,我们测定了4月龄和24月龄白化Wistar大鼠大脑和血浆中的脂质过氧化水平、抗氧化酶活性、乙酰胆碱酯酶(AChE)活性以及大脑中的生物胺水平。结果显示,老年大鼠大脑和血浆中的脂质过氧化水平显著高于年轻大鼠。抗氧化酶活性在大脑和血浆中均呈现出年龄依赖性下降。老年大鼠大脑和血浆中的谷胱甘肽过氧化物酶和过氧化氢酶活性显著降低。老年大鼠血浆中的超氧化物歧化酶(SOD)也显著降低;然而,大脑中SOD也有下降趋势(不显著)。老年大鼠大脑和血浆中的AChE活性显著降低。本研究通过莫里斯水迷宫(MWM)和高架十字迷宫(EPM)试验评估大鼠的学习和记忆能力。老年大鼠的短期记忆和长期记忆均显著受损,这在MWM中潜伏期显著延长以及EPM中转位潜伏期增加中明显体现。此外,老年大鼠大脑中的生物胺(去甲肾上腺素、多巴胺和5-羟色胺)也显著减少。总之,我们的数据表明,老年大鼠大脑中氧化应激增加、抗氧化酶活性下降、AChE活性改变以及生物胺水平降低可能与记忆功能减退有关。

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