title: Protein kinase C mediates amyloid beta-protein fragment 31-35-induced suppression of hippocampal late-phase long-term potentiation in vivo.
abstract: Amyloid beta-protein (Abeta) in the brain of Alzheimer's disease (AD) plays a detrimental role in synaptic plasticity and cognitive function. The effects of Abeta on the early-phase long-term potentiation (E-LTP) have been reported widely. However, whether the late-phase long-term potentiation (L-LTP), which differs from E-LTP mechanistically, is also affected by Abeta is still an open question. The present study examined the effects of intracerebraventricular injection of Abeta fragments 25-35 and 31-35 on the L-LTP in the CA1 area of rat hippocampus in vivo, and further investigated its possible underlying mechanism. Our results showed that: (1) Abeta25-35 (6.25-25 nmol) did not affect the baseline field excitatory postsynaptic potentials, but dose-dependently suppressed multiple high-frequency stimuli-induced L-LTP; (2) Abeta31-35, a shorter Abeta fragment than Abeta25-35, also significantly suppressed L-LTP, with the same suppressive effects as Abeta25-35; (3) pretreatment with PMA (6 nmol/5 microl), a membrane permeable PKC agonist, effectively prevented Abeta31-35-induced deficits in the early and the late components of L-LTP; (4) co-application of Abeta31-35 and chelerythrine (12 nmol/5 microl), a PKC antagonist, caused no additive suppression of L-LTP. These results indicate that both Abeta25-35 and Abeta31-35 can impair hippocampal synaptic plasticity in vivo by suppressing the maintenance of L-LTP, and PKC probably mediates the Abeta-induced suppression of hippocampal L-LTP. In addition, the similar efficacy of Abeta31-35 and Abeta25-35 in L-LTP suppression supports the hypothesis we suggested previously that the sequence 31-35 in Abeta might be the shortest active sequence responsible for the neuronal toxicity induced by full length of Abeta molecules.
authors.affiliation: Department of Neurobiology and National Key Discipline of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zhang
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D004567:Electrodes, Implanted; D020536:Enzyme Activators / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D053119:Benzophenanthridines; D020536:Enzyme Activators; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35); C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate