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戊四氮点燃小鼠的年龄依赖性学习和记忆缺陷。

Age dependent learning and memory deficit in Pentylenetetrazol kindled mice.

机构信息

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, Punjab, India.

出版信息

Eur J Pharmacol. 2012 Jan 15;674(2-3):315-20. doi: 10.1016/j.ejphar.2011.11.010. Epub 2011 Nov 24.

Abstract

Epilepsy is a chronic neurological disorder and well documented to induce cognitive impairment. Further onset of epilepsy at different age levels have different effect on cognitive function. Kindling has been used to model clinical epilepsy to study different psychiatric and neurological changes associated with it. Only one study has been reported for age dependent learning deficit in kindled rats but till date no such study is available for mice. Therefore this study was envisaged to find out the correlation of age of mice with feasibility for induction and resistance to kindling and learning and memory deficits. In this study, kindling was induced by administration of subconvulsive dose of pentylenetetrazol (35 mg/kg; i.p.) on alternate days in mice of different age group (2, 6 and 12 month old). For the evaluation of short term, long term spatial and contextual fear memory Elevated Plus Maze and Passive Shock Avoidance Paradigm were used respectively. Induction of kindling significantly impaired learning and memory in different age group of mice as compared to their naïve. Kindling also affected the working and reference spatial memory, with function of age in kindled mice, and contextual fear memory in kindled mice, however not in age dependent manner. Thus the present study validated the existence of age dependent differences in learning and memory deficit and induction of kindling in mice. Results suggested suitability of 6 month old mice for long term neuropharmacological studies pertaining to epilepsy associated cognitive deficit with adequate memory deficit and insignificant resistance to kindling and mortality.

摘要

癫痫是一种慢性神经障碍,有充分的文献记载表明它会导致认知障碍。进一步地,在不同年龄阶段发作的癫痫对认知功能有不同的影响。点燃已被用于模拟临床癫痫,以研究与之相关的不同精神和神经变化。只有一项研究报告了点燃大鼠的年龄依赖性学习缺陷,但迄今为止,尚无关于小鼠的此类研究。因此,本研究旨在探讨与年龄相关的小鼠的可行性,以及与点燃、学习和记忆缺陷的易感性和抗性之间的相关性。在这项研究中,通过在不同年龄组(2、6 和 12 个月大)的小鼠中隔日给予亚惊厥剂量的戊四氮(35mg/kg;ip)来诱导点燃。为了评估短期、长期空间和情境恐惧记忆,分别使用高架十字迷宫和被动回避回避范式。与未处理的小鼠相比,点燃显著损害了不同年龄组小鼠的学习和记忆能力。点燃还影响了工作和参考空间记忆,以及点燃小鼠的情境恐惧记忆,但不是以年龄依赖的方式。因此,本研究验证了在学习和记忆缺陷以及在小鼠中诱导点燃方面存在年龄依赖性差异。结果表明,6 个月大的小鼠适合进行与癫痫相关认知缺陷相关的长期神经药理学研究,具有足够的记忆缺陷和对点燃的抗性和死亡率没有显著影响。

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