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Peptide Fragments of β‐Amyloid Precursor Protein: Effects on Parallel Fiber‐Purkinje Cell Synaptic Transmission in Rat Cerebellum
Author(s) -
Hartnell Nick A.,
Suh Y. H.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.741112.x
Subject(s) - purkinje cell , ampa receptor , parallel fiber , neurotransmission , cerebellum , neuroscience , cerebellar cortex , chemistry , microbiology and biotechnology , biology , biophysics , biochemistry , glutamate receptor , receptor
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 (CT 105 ) of βAPP to discrete dendritic regions of intact Purkinje cells. βAPP and the amyloid β (Aβ) peptide fragments Aβ 1‐16 , Aβ 25‐35 , 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.