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 -Peptide A-25-35 Blocks Adenylate Cyclase-Mediated Forms of Hippocampal Long-Term Potentiation
a Program in Molecular Biology, Pomona College, Claremont, California, USA b Program in Neuroscience and Department of Biology, Pomona College, Claremont, California, USA
Key Words:  -amyloid peptide • A25-35 • long-term potentiation • hippocampus • adenylate cyclase
Address for correspondence: Karen D. Parfitt, Ph. D., Department of Biology, Pomona College, 175 W. Sixth St., Claremont, CA 91711. Voice: 909-621-8604; fax: 909-621-8878. kparfitt{at}pomona.edu
Progressive memory loss and deposition of amyloid
(A) peptides throughout cortical regions are hallmarks of Alzheimer's disease (AD). Several studies in mice and rats have shown that overexpression of amyloid precursor protein (APP) or pretreatment with A peptide fragments results in the inhibition of hippocampal long-term potentiation (LTP) as well as impairments in learning and memory of hippocampal-dependent tasks. For these studies we have investigated the effects of the A25-35 peptide fragment on LTP induced by adenylate cyclase stimulation followed immediately by application of Mg++-free aCSF ("chemLTP"). Treatment of young adult slices with the A25-35 peptide had no significant effect on basal synaptic transmission in area CA1, but treatment with the peptide for 20 min before inducing chemLTP with isoproterenol (ISO; 1 µM) or forskolin (FSK;10 µM) + Mg++-free aCSF resulted in complete blockade of LTP. In contrast, normal ISO-chemLTP was observed after treatment with the control peptide A35-25. The ability of the A25-35 peptide fragment to block this and other forms of synaptic plasticity may help elucidate the mechanisms underlying hippocampal deficits observed in animal models of AD and/or AD individuals.
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