title: Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability.
abstract: β-amyloid protein (Aβ) accumulation in cerebral centers involved in cognition and memory is a pivotal pathological feature of Alzheimer's disease (AD). The onset process of type 2 diabetes mellitus (T2DM) has a number of similarities compared with AD. Thus, it is hypothesized that the pharmacological therapy employed for the treatment of T2DM may help to prevent and ameliorate the symptoms of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 analogue which is used as a therapeutic drug for T2DM, markedly antagonized Aβ fragment-induced attenuation of spatial learning and memory ability, as indicated by a Morris water maze experiment. In addition, we investigated the potential underlying electrophysiological and molecular mechanisms. The results indicate that Exendin-4 rescued long-term potentiation from Aβ1-42-induced damage in the rat hippocampal CA1 regionin vivo, and antagonized Aβ1-42-induced reduction of cyclic adenosine monophosphate and phosphorylated-cAMP response element-binding protein in rat hippocampal tissue using ELISA and western blot analysis, respectively. Thus, the results of the present study provide theoretical support for the application of Exendin-4 for improving AD.
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
keywords: Exendin-4; mechanism; neuroprotection; β-amyloid protein 1-42