摘要
目的探讨抗癫痫药托吡酯(TPM)对幼鼠学习记忆能力的影响及其可能机制。方法 10 d龄Sprague-Dawley(SD)幼鼠60只随机分为4组:短程对照组(n=10)、长程对照组(n=10)、TPM短程组(n=20)及TPM长程组(n=20);TPM短程组及长程组均予TPM 40 mg·kg-1·d-1灌胃,对照组予等容量生理盐水灌胃;满时程后运用Y-型迷宫观察各组幼鼠学习记忆能力的变化,光镜下观察其海马区结构变化,并用免疫组织化学法检测海马区5-羟色胺(5-HT)和γ-氨基丁酸(GABA)的表达。结果(1)TPM短程组与短程对照组比较,幼鼠海马区神经元形态学无改变;学习记忆能力无明显差异[分别为(27.00±3.64)次,(25.00±2.30次);(88.00±1.89)%,(90.00±1.96)%,P>0.05];5-HT免疫阳性神经元数量及GABA免疫阳性神经元数量变化均无明显差异[分别为(23.85±2.30)个,(25.40±3.06)个;(9.40±1.57)个,(8.50±1.08)个,P>0.05]。(2)TPM长程组与长程对照组比较,幼鼠海马区存在形态学改变;学习记忆能力较其对照组降低,其差异有统计学意义[分别为(40.00±2.98)次,(24.00±2.22)次;(69.00±3.53)%,(89.00±2.45)%,P<0.01];5-HT免疫阳性神经元数量较其对照组明显降低[(14.20±2.71)个,(26.10±2.23)个],GABA免疫阳性神经元数量较其对照组增高[(21.25±1.80)个,(8.60±1.43)个],其差异均有统计学意义(P<0.01)。结论 TPM对幼鼠学习记忆能力存在损害,其损害程度可能与TPM的应用时间有关;TPM引起的学习记忆能力损害可能与海马区5-HT水平降低及GABA活性增加有关。
Objective To observe effects of topiramate on the ability of learning and memory in immature rats and investigate the possible mechanism. Methods A total of 60 healthy 10-day-old Sprague-Dawley（SD） rats pups were assigned into 4 groups randomly： short-term control group （n = 10） , long-term control group （n = 10）, TPM short-term group（n =20） and TPM long-term group（ n = 20）. The rats in TPM short-term group and TPM long-term group were received intragastric administration of TPM （40 mg· kg^-1· d^-1 ） , and the rats in short-term control group and long-term control group were handled by injection of normal saline NS with the same volume into stomach. All performances were undertaken 2 times a day. The ethology features of spatial learning and memory that emerged in the γ-Water Maze were observed. The immunoreactivity of 5-hydroxytryptamine and γ-aminobutyric acid in the brain was investigated. Results （ 1 ） There were no significant differences both in the change of histomorphology of rat＇ s brain and the ability of learning and memory that rat emerged between control group and TPM group for short term [ （27.00 ± 3.64） vs （25.00 ± 2.30） ; （88.00 ± 1.89） % vs （90.00 ± 1.96% ）, P 〉 0.05 ] ; and there were also no significant differences in the the number of 5-HT and GABA positive neuron in immunoreactivity between control group and TPM group for short term [ （23.85 ± 2.30 ） vs （ 25.40 ± 3.06 ） ; （ 9.40 ± 1.57 ） vs （ 8.50 ± 1.08 ） , P 〉 0.05 ]. （ 2 ） The morphological and histological change could be observed and the ability of learning and memory that rat emerged of TPM group for long period were decreased obviously compared with the control group [ （40 ± 2.98 ） vs （24 ± 2.22） ; （69 ± 3.53 ） % vs （ 89 ± 2.45 ） %, P 〈 0.01 1. The quantity of 5-HT positive neuron in immunoreactivity of TPM group for long period was decreased obviously compared with the control group [ （ 14.20 ± 2.71 ） vs （ 26.10± 2.23 ）, P 〈 0.01 ], and the quantity of GABA positive neuron in ilnmunoreac- tivity was more higher than control group [ （21.25 ± 1.80） vs （ 8.60 ± 1.43 ）, P 〈 0.01 ]. Conclusions TPM affects the ability of learning and memory in immature rats, and the degree of the effect may be related to the time course of the medication. The cognitive functional impairment caused by TPM may be concerned with the decrease of 5-HT and the increase of GABA activity in rats hippocampus.
出处
《中华脑科疾病与康复杂志（电子版）》
2011年第1期12-14,共3页
Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）
基金
河南省教育厅基金项目(2010B320014)
关键词
托吡酯
学习记忆
5-羟色胺
γ-氨丁酸
Topiramate
Learning and memory
5-hydroxytryptamine
γ-aminobutyric acid
