快速老化小鼠的学习记忆缺陷及其生化机制

目的用快速老化小鼠(SAMP8)模拟老年痴呆,观察其学习记忆能力,并探讨其学习记忆能力下降的可能机制。方法采用10月龄SAMP8,并用同龄抗快速老化小鼠(SAMR1)作为正常对照。用水迷路检测近记忆以及空间学习记忆能力。用生物化学方法检测大脑皮层线粒体膜电位和ATP酶活力,观察线粒体功能;检测皮层和海马胆碱乙酰基转移酶(ChAT)和乙酰胆碱酯酶(AChE)的活力,观察中枢胆碱能神经功能;检测血清超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量,观察其全身性氧化应激状况。结果与SAMR1相比,SAMP8出现明显的衰老体征,其近记忆和空间学习记忆能力明显减弱,具有衰老和痴呆特征;皮层线粒体膜电位和ATP酶活力显著降低,海马ChAT活力显著下降,AChE活力显著升高,血清SOD活力稍有增高。结论SAMP8可以很好地模拟老年痴呆,其机制包括大脑皮层线粒体功能降低、海马胆碱能神经功能下降以及氧化应激等。

Learning and memory deficits in SAMP8 and their biochemical mechanisms

Objective To simulate senile dementia with senescence-accelerated mouse/prone 8(SAMP8) and investigate its learning and memory deficits,and their biochemical mechanisms.Methods The general status of SAMP8 was investigated compared with that of SAM/resistance 1(SAMR1).Then their recent memory and spatial learning and memory abilities were detected with water maze.The mitochondrial membrane potential and adenosine triphosphatase(ATPase) of cortex were determined with biochemical method to investigate their mitochondrial function.The choline acetyltransferase(ChAT) and acetylcholinesterase(AChE) activities of cortex and hippocampus were detected with the above method to observe their central cholinergic nerve function.The superoxide dismutase(SOD) activity and malondialdehyde(MDA) content in serum of mice were determined with biochemical method to observe their general oxidative stress.Results Compared with SAMR1,SAMP8 displayed significant senile physical signs,and weak recent memory and spatial learning and memory capabilities were similar to those characteristics of senescence and dementia.Meanwhile,the mitochondrial membrane potential and ATPase activity of cortex,and the ChAT activity of hippocampus were lower than those of SAMR1,but the AChE activity of hippocampus was higher than that of SAMR1,and the serum SOD activity was slightly higher than that of SAMR1.Conclusion SAMP8 may simulate senile dementia and its pathogenesis involves insufficient cortex mitochondrial function,decreased cholinergic nerve function,and oxidative stress.