Cargando…

Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability

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 pharmacol...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xiaohui, Wang, Li, Jiang, Ruirui, Xu, Yunyun, Zhao, Xueling, Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103720/
https://www.ncbi.nlm.nih.gov/pubmed/27882091
http://dx.doi.org/10.3892/etm.2016.3742
_version_ 1782466639654027264
author Wang, Xiaohui
Wang, Li
Jiang, Ruirui
Xu, Yunyun
Zhao, Xueling
Li, Yang
author_facet Wang, Xiaohui
Wang, Li
Jiang, Ruirui
Xu, Yunyun
Zhao, Xueling
Li, Yang
author_sort Wang, Xiaohui
collection PubMed
description 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 region in 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.
format Online
Article
Text
id pubmed-5103720
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-51037202016-11-23 Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability Wang, Xiaohui Wang, Li Jiang, Ruirui Xu, Yunyun Zhao, Xueling Li, Yang Exp Ther Med Articles 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 region in 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. D.A. Spandidos 2016-11 2016-09-21 /pmc/articles/PMC5103720/ /pubmed/27882091 http://dx.doi.org/10.3892/etm.2016.3742 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Xiaohui
Wang, Li
Jiang, Ruirui
Xu, Yunyun
Zhao, Xueling
Li, Yang
Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title_full Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title_fullStr Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title_full_unstemmed Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title_short Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability
title_sort exendin-4 antagonizes aβ1-42-induced attenuation of spatial learning and memory ability
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103720/
https://www.ncbi.nlm.nih.gov/pubmed/27882091
http://dx.doi.org/10.3892/etm.2016.3742
work_keys_str_mv AT wangxiaohui exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability
AT wangli exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability
AT jiangruirui exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability
AT xuyunyun exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability
AT zhaoxueling exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability
AT liyang exendin4antagonizesab142inducedattenuationofspatiallearningandmemoryability