title: Involvement of P38MAPK activation by NMDA receptors and non-NMDA receptors in amyloid-β peptide-induced neuronal loss in rat hippocampal CA1 and CA3 subfields.
abstract: Oligomeric amyloid-β peptide (Aβ) has been found to be associated with the pathogenesis of Alzheimer's disease (AD). Numerous studies have reported Aβ neurotoxicity, but the underlying molecular mechanisms remain to be fully illuminated. In the present study, we investigated the Aβ-induced activation and regulation of P38MAPKs in rat hippocampus in vivo. The results showed that intracerebroventricular injection of oligomeric Aβ25-35 increased the activation (phosphorylation) of P38MAPKs, and the level of cleaved caspase-3, but decreased the number of neurons in rat hippocampal CA1 and CA3 subfields. Downregulation of P38MAPK activity by SB239063 protected against the Aβ neurotoxicity. Pretreatment with NMDA and non-NMDA receptor antagonists respectively suppressed P38MAPK activation induced by Aβ25-35 oligomers and presented neuroprotective effect. Taken together, these data suggest that P38MAPK activation via NMDA and non-NMDA receptors is a key signal cascade in Aβ-induced neuronal death. Inhibition of P38MAPK cascades may be a promising treatment in AD.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Jiangsu, China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, China; Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, China; Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Jiangsu, China.
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, China; Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Jiangsu, China.
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Jiangsu, China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, China; Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Jiangsu, China. Electronic address: xyhou@xzmc.edu.cn.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Hou
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C074636:amyloid beta-protein (25-35); D048051:p38 Mitogen-Activated Protein Kinases
keywords: Alzheimer's disease; Amyloid-β peptide; NMDA receptors; Non-NMDA receptors; P38MAPKs