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拉莫三嗪可减轻阿尔茨海默病样小鼠模型中的炎症反应并改善执行功能衰退

Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model.

作者信息

Wang Kexin, Fernandez-Escobar Alejandro, Han Shuhong, Zhu Ping, Wang Jun-Hui, Sun Yu

机构信息

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.

School of Medicine, CES University, Medellin, Antioquia, Colombia.

出版信息

Biomed Res Int. 2016;2016:7810196. doi: 10.1155/2016/7810196. Epub 2016 Nov 30.

Abstract

Alzheimer's disease (AD) has been described in the literature, to be associated with impairment of executive function which develops early in the course of disease, and an effective treatment for this clinical feature remains elusive. Preclinical studies have implied that lamotrigine, an antiepileptic agent, could be a potential treatment for executive dysfunction in AD patients. Although there have been promising results in previous studies with lamotrigine, executive function has never been measured using animal models. The aim of the present study was to evaluate the effects of lamotrigine on executive function and determine whether lamotrigine can attenuate inflammatory response in an AD mouse model. Nontransgenic and transgenic mice were treated with lamotrigine (0 or 30 mg/kg/day) in a standard laboratory chow diet starting at 3 months of age. After 6 months of continuous lamotrigine administration, there was a marked improvement in executive function and a significant attenuation in the expression of proinflammatory cytokines. These results suggest that lamotrigine could ameliorate executive dysfunction and brain inflammatory response in the mouse model of AD and early lamotrigine intervention may be a promising therapeutic strategy for AD.

摘要

文献中已描述,阿尔茨海默病(AD)与疾病早期出现的执行功能障碍有关,而针对这一临床特征的有效治疗方法仍未找到。临床前研究表明,抗癫痫药物拉莫三嗪可能是治疗AD患者执行功能障碍的一种潜在药物。尽管之前关于拉莫三嗪的研究取得了有前景的结果,但从未使用动物模型来测量执行功能。本研究的目的是评估拉莫三嗪对执行功能的影响,并确定拉莫三嗪是否能减轻AD小鼠模型中的炎症反应。非转基因和转基因小鼠从3月龄开始,在标准实验室饲料中接受拉莫三嗪(0或30mg/kg/天)治疗。连续给予拉莫三嗪6个月后,执行功能有显著改善,促炎细胞因子的表达也明显降低。这些结果表明拉莫三嗪可改善AD小鼠模型中的执行功能障碍和脑部炎症反应,早期拉莫三嗪干预可能是AD的一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/154f/5155079/f0280298e2ed/BMRI2016-7810196.001.jpg

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