3-methyladenine, an autophagic inhibitor, attenuates therapeutic effects of sirolimus on scopolamine-induced cognitive dysfunction in a rat model

被引：0
作者：
Zhu, Bin [1 ]
Yang, Chun [1 ]
Ding, Liang-Cai [1 ]
Liu, Ning [1 ]
机构：
[1] Soochow Univ, Affiliated Hosp 3, Dept Crit Care Med, Changzhou 213003, Jiangsu, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2014年 / 7卷 / 10期
关键词：
3-methyladenine; autophagy; sirolimus; scopolamine; cognitive dysfunction; ALZHEIMERS-DISEASE; MAMMALIAN TARGET; RAPAMYCIN; NEURODEGENERATION; IMPAIRMENT; DEFICITS; BACE1; MTOR;
D O I：
暂无
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Previous studies have demonstrated that sirolimus has therapeutic effects for Alzheimer's disease which characterized by cognitive dysfunction. However, its underlying mechanisms have not been fully elucidated. In the present study, we aimed to investigate the mechanisms of therapeutic effects of sirolimus for cognitive dysfunction rat model which induced by chronic administration of scopolamine. Forty Wistar rats were randomly divided into 4 groups (n=10 each): saline group and scopolamine group, sirolimus plus scopolamine group and 3-methyladenine pretreatment group. Morris water maze test was applied to measure the cognitive function of rat. After behavioral test, rats were sacrificed and prefrontal cortex and hippocampus were harvested for measuring amyloid-beta (A beta), Beclin-1 and mammalian target of rapamycin (mTOR). Compared with saline group, scopolamine administered significantly decreased the cognitive performance of rats during the Morris water maze test and changed A beta, Beclin-1 and mTOR levels in rat prefrontal cortex and hippocampus (P<0.05); In addition, rats in sirolimus plus scopolamine group significantly reversed scopolamine-induced effects (P<0.05). Most importantly, 3-methyladenine abrogated the effects of sirolimus on scopolamine-induced cognitive dysfunction (P<0.05). In conclusion, the mechanism of sirolimus exerting therapeutic effects for scopolamine-induced cognitive dysfunction is likely related to the activation of autophagy.
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页码：3327 / 3332
页数：6
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