title: Exendin-4 antagonizes Aβ1-42-induced suppression of long-term potentiation by regulating intracellular calcium homeostasis in rat hippocampal neurons.
abstract: An imbalance of intracellular calcium homeostasis induced by amyloid β-protein (Aβ) contributes to the pathogenesis of Alzheimer's disease (AD), such as deficits in learning and memory. Therefore, regulation of calcium homeostasis may represent a new strategy for treatment of AD. Growing evidence suggests that type 2 diabetes mellitus (T2DM) and AD are closely related in pathogenesis. Thus, drugs used in treatment of T2DM may modify the pathogenesis of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 (GLP-1) analog used as a therapeutic drug for T2DM, significantly antagonized suppression of long-term potentiation (LTP) induced by Aβ1-42 in the rat hippocampal CA1 region in vivo. This neuroprotection may be mediated by regulation of calcium homeostasis. Pretreatment with Exendin-4 suppressed Aβ1-42-induced elevation in intracellular calcium concentration ([Ca(2+)]i) through L-type voltage-dependent calcium channels (L-VDCCs) and N-methyl-D-aspartate receptors (NMDARs). Furthermore, Exendin-4 antagonized the decrease in p-Ca(2+)/calmodulin-dependent protein kinase IIα (p-CaMKIIα) induced by Aβ1-42 in the rat hippocampal CA1 region. Thus, the neuroprotective effects of Exendin-4, which likely involve regulation of calcium homeostasis, provide theoretical support for using Exendin-4 to treat and prevent AD in the future.
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: 163.wangxh@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Morphology Laboratory, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Yameng
authors.initials: Y
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077270:Exenatide; D006624:Hippocampus / Q000166:cytology*; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C075222:amyloid beta-protein (1-42); C056639:2-amino-5-phosphopentanoic acid; D000077270:Exenatide; D014633:Valine; D009543:Nifedipine; D002118:Calcium
keywords: Aβ1-42; Calcium homeostasis; Exendin-4; Neuroprotection