title: Aβ induces acute depression of excitatory glutamatergic synaptic transmission through distinct phosphatase-dependent mechanisms in rat CA1 pyramidal neurons.
abstract: Beta-amyloid peptide (Aβ) has a causal role in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that Aβ can disrupt excitatory glutamatergic synaptic function at synaptic level. However, the underlying mechanisms remain obscure. In this study, we recorded evoked and spontaneous EPSCs in hippocampal CA1 pyramidal neurons via whole-cell voltage-clamping methods and found that 1 μM Aβ can induce acute depression of basal glutamatergic synaptic transmission through both presynaptic and postsynaptic dysfunction. Moreover, we also found that Aβ-induced both presynaptic and postsynaptic dysfunction can be reversed by the inhibitor of protein phosphatase 2B (PP2B), FK506, whereas only postsynaptic disruption can be ameliorated by the inhibitor of PP1/PP2A, Okadaic acid (OA). These results indicate that PP1/PP2A and PP2B have overlapping but not identical functions in Aβ-induced acute depression of excitatory glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons.
authors.affiliation: Department of Pharmacology, Wuxi Higher Health Vocational Technology School, Wuxi, Jiangsu Province, People's Republic of China. ywen1985@yahoo.com.cn
authors.forename: Wen
authors.initials: W
authors.lastname: Yao
authors.forename: Hao-Jun
authors.initials: HJ
authors.lastname: Zou
authors.forename: Da
authors.initials: D
authors.lastname: Sun
authors.forename: Si-Qiang
authors.initials: SQ
authors.lastname: Ren
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D019703:Calcineurin / Q000502:physiology*; D065095:Calcineurin Inhibitors; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D065095:Calcineurin Inhibitors; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D018698:Glutamic Acid; D019703:Calcineurin; D016559:Tacrolimus