Open AccessIncrease of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor.
Author(s) -
JeanMarc Roch,
Eliezer Masliah,
AnneCatherine RochLevecq,
Mary Sundsmo,
Deborah A. C. Otero,
Isaac Veinbergs,
Tsuano Saitoh
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.16.7450
Subject(s) - neurite , amyloid precursor protein , peptide , neuroscience , neuropil , chemistry , microbiology and biotechnology , biochemistry , biology , endocrinology , alzheimer's disease , medicine , in vitro , central nervous system , disease
The secreted form (sAPP) of the Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in the in vitro regulation of fibroblast growth and neurite extension from neuronal cells. The active site of sAPP responsible for these functions is within a small domain just C-terminal to the Kunitz-type protease inhibitor (KPI) insertion site. We report here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infused into rat brains. After 2 weeks of APP 17-mer peptide infusion, the animals were tested for reversal learning and memory retention and were sacrificed for morphological examination of brains. We found that administration of the APP 17-mer peptide resulted in an 18% increase in the number of presynaptic terminals in the frontoparietal cortex. At the behavioral level, 17-mer-infused animals with nonimpaired learning capability showed an increased memory retention that seemed to interfere with reversal learning performance. This APP 17-mer effect on memory retention was not observed in animals with impaired initial learning capacity. These results suggest that APP is involved in memory retention through its effect on synaptic structure.