摘要
目的 研究长期应用托吡酯(TPM)对认知功能的影响及其机制。方法 不同剂量的TPM给予锂—匹罗卡品致痫幼鼠模型,Morris水迷宫试验评价大鼠视觉空间学习记忆能力的变化,用多相寡核苷酸探针通过原位杂交法观察海马各区域代谢型谷氨酸受体亚型1(mGluR1)mRNA的表达变化,并与对照组比较。结果与对照组相比,给予大剂量(80 mg/kg)TPM显著抑制了模型和非模型幼鼠的视觉空间学习记忆能力,中小剂量者影响不明显。大剂量TPM模型组海马CA1～CA3区mGluR1mRNA的表达显著下调。结论长期大剂量应用TPM可能损害认知功能,海马CA1区mGluR1mRNA的表达下调是其影响认知功能的可能途径之一。
Objective The purpose of the study was to investigate learning and memory alteration exposed to long-term topiramate (TPM) treatment and the possible mechanism in terms of metabotropic glutamate receptor subtypel (mGluR1) mRNA expression in hippocampus. Methods Visual-spatial performance was assessed with Morris water maze test before and after various dose of TPM treatment in lithium-pilocarpine seizure model. In situ hybridization with digoxin-labelled multiphase oligonucleotide probes was used to determine hippocampus mGluR1mRNA expression. Results Significant memory dysfunction was observed in rat model treated with high dose(80 mg/d for 28 d) TPM, meanwhile in hippocampal CA1 region, down-regulated mGluR1 mRNA expression was observed. Conclusions Our data implied that long-term and high-dose of TPM treatment may cause cognitive deficits. Down-regulated mGluRlmRNA expression in hippocampal CA1 may be involved in TPM induced cognitive deficits.
出处
《卒中与神经疾病》
2003年第6期352-355,共4页
Stroke and Nervous Diseases
