标题:Sitagliptin protects the cognition function of the Alzheimer's disease mice through activating glucagon-like peptide-1 and BDNF-TrkB signalings
作者:Dong, Qing; Teng, Shuai-Wen; Wang, Yue; Qin, Feng; Li, Yue; Ai, Lu-Lu; Yu, Hui
作者机构:[Dong, Qing; Ai, Lu-Lu] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China.; [Teng, Shuai 更多
通讯作者:Dong, Q;Yu, H
通讯作者地址:[Dong, Q]Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China;[Yu, H]Shandong Univ, Sch Basic 更多
来源:NEUROSCIENCE LETTERS
出版年:2019
卷:696
页码:184-190
DOI:10.1016/j.neulet.2018.12.041
关键词:Sitagliptin; Alzheimer's disease; Cognitive function; Synaptic; plasticity; TrkB signaling
摘要:Bacicground: Sitagliptin is an anti-diabetic drug and its effects on Alzheimer's disease (AD) remain controversial. This study aimed to investigate the protective effect of sitagliptin on the cognition in AD and its underlying molecular mechanism.; Methods: The APP/PS1 (a model of AD) mice received daily gastric gavage administration of sitagliptin (20 mg/kg) for 8 weeks. Then animals were subjected to behavioral experiment or sacrificed to histological staining and protein level analysis.; Results: The MWM test showed that sitagliptin treatment significantly reduced the escape latency times in APP/ PS1 mice in the learning phase (day 3-5) and elongated the time spent in the target quadrant in the probe test. Sitagliptin significantly reduced amyloid plaque deposition and elevated the spine density and the protein levels of synaptoneurosome GluA1- and GluA2-containing AMPA receptor (GluA1R and GluA2R) in the brain of the APP/PS1 mice. Sitagliptin treatment significantly up-regulated the brain BNDF protein and phosphorylation of tyrosine receptor kinase B (TrkB). Furthermore, exendin-(9-39) (a glucagon-like peptide-1 [GLP-1] receptor antagonist) and K252a (a Trk tyrosine kinase inhibitor) treatment significantly abolished the cognitive protective effect of sitagliptin in the MWM test.; Conclusion: Sitagliptin treatment effectively protected the cognition function of the AD mice by regulating synaptic plasticity, at least partially, through activating GLP-1 and BDNF-TrkB signalings.
收录类别:SCOPUS;SCIE
WOS核心被引频次:1
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059297967&doi=10.1016%2fj.neulet.2018.12.041&partnerID=40&md5=879916d15532b82c160e5b45254f99ce
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