title: Exendin-4, a glucagon-like peptide 1 receptor agonist, protects against amyloid-β peptide-induced impairment of spatial learning and memory in rats.
abstract: Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share specific molecular mechanisms, and agents with proven efficacy in one may be useful against the other. The glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has similar properties to GLP-1 and is currently in clinical use for T2DM treatment. Thus, this study was designed to characterize the effects of exendin-4 on the impairment of learning and memory induced by amyloid protein (Aβ) and its probable molecular underlying mechanisms. The results showed that (1) intracerebroventricular (i.c.v.) injection of Aβ1-42 resulted in a significant decline of spatial learning and memory of rats in water maze tests; (2) pretreatment with exendin-4 effectively and dose-dependently protected against the Aβ1-42-induced impairment of spatial learning and memory; (3) exendin-4 treatment significantly decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl2 in Aβ1-42-induced Alzheimer's rats. The vision and swimming speed of the rats among all groups in the visible platform tests did not show any difference. These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the behavioral impairment induced by neurotoxic Aβ1-42, and the underlying protective mechanism of exendin-4 may be involved in the Bcl2, Bax and caspase-3 pathways. Thus, the application of exendin-4 or the activation of its signaling pathways may be a promising strategy to ameliorate the degenerative processes observed in AD.
authors.affiliation: Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China.
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Jia
authors.affiliation: Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China.
authors.lastname: Ye-Tian
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China.
authors.lastname: Yuan-Li
authors.affiliation: Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China.
authors.forename: Ge-Juan
authors.initials: GJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China.
authors.forename: Zheng-Li
authors.initials: ZL
authors.lastname: Di
authors.affiliation: Department of Pathology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ying
authors.affiliation: Department of Pathology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Biology, York University, Toronto, ON M3J 1P3, Canada.
authors.forename: Er-Fei
authors.initials: EF
authors.lastname: Song
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: jinshunqi2009@163.com.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
authors.affiliation: Department of Pathology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China. Electronic address: panyanfang2000@163.com.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Pan
mesh_terms: D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects* / Q000502:physiology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: Amyloid-β peptide; Bcl2/Bax; Caspase-3; Exendin-4; Spatial learning and memory