title: Pyruvate prevents the inhibition of the long-term potentiation induced by amyloid-β through protein phosphatase 2A inactivation.
abstract: Amyloid-β (Aβ) oligomers are derived from proteolytic cleavage of amyloid-β protein precursor and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. Pyruvate has a protective effect against Aβ-induced neuronal cell death in hippocampal slice cultures. However, whether pyruvate also has a protective effect against the inhibition of neuronal plasticity induced by Aβ remains to be elucidated. This study examined the effect of pyruvate on the Aβ-induced inhibition of LTP in the rat hippocampus. We found that pyruvate prevented the Aβ-induced inhibition of LTP as strong as fostriecin, a specific protein phosphatase 2A (PP2A) inhibitor. Pyruvate prevented the Aβ block of Ca(2+)/calmodulin dependent protein kinase 2 (CaMK2) autophosphorylation and the Aβ-induced PP2A activation. Pyruvate, but not lactate, decreased reactive oxygen species levels in CA1 slices exposed to Aβ. We propose that pyruvate could prevent the Aβ-induced inhibition of LTP by the re-autophosphorylation of CaMK2 through PP2A inactivation. The reduction of reactive oxygen species production is considered to be the upstream mechanism of this observed pyruvate protection.
authors.affiliation: Department of Gerontology and Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, China. wxiaon9981@yahoo.co.jp
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takata
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Bai
authors.forename: Fengrong
authors.initials: F
authors.lastname: Ou
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokono
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D011090:Polyenes; D011753:Pyrones; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054648:Protein Phosphatase 2; C040313:fostriecin