Peptide Fragments of β-Amyloid Precursor Protein: Effects on Parallel Fiber-Purkinje Cell Synaptic Transmission in Rat Cerebellum

Authors

  • Nick A. Hartnell,

    1. Pharmaceutical Science Research Institute, Aston University, Birmingham, England Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea
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  • Y. -H. Suh

    1. Pharmaceutical Science Research Institute, Aston University, Birmingham, England Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea
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Address correspondence and reprint requests to Dr. N. A. Hartell at Pharmaceutical Sciences Research Institute, Aston University, Aston Triangle, Birmingham B4 7ET, U.K. E-mail: n.a.hartell@aston.ac.uk

Abstract

The effects of peptide fragments of the β-amyloid precursor protein (βAPP) on parallel fiber (PF)-Purkinje cell synaptic transmission in the rat cerebellum were examined. Transient inward currents associated with calcium influx were induced by localized applications of the 105-amino acid carboxy-terminal fragment (CT105) of βAPP to discrete dendritic regions of intact Purkinje cells. βAPP and the amyloid β (Aβ) peptide fragments Aβ1-16, Aβ25-35, and Aβ1-42 had little or no effect. Inward currents were also observed following applications of CT105 to isolated patches of somatic Purkinje cell membrane. All five proteins/peptides induced some depression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor-mediated synaptic transmission between PFs and Purkinje cells, through a combination of pre- and postsynaptic effects. CT105 induced the greatest depression, which spread to distant synapses following local application and which was prevented by inhibition of nitric oxide synthase. These data indicate that CT fragments of the βAPP can modulate AMPA-mediated glutamatergic synaptic transmission in the cerebellar cortex. These fragments may therefore be considered alternative candidates for some of the neurotoxic effects of Alzheimer's disease.

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