Journal
NEUROBIOLOGY OF DISEASE
Volume 26, Issue 1, Pages 282-290Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.01.005
Keywords
cellular prion protein; STI1; memory; learning
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Cellular prion protein (PrPC) is a cell surface glycoprotein that interacts with several ligands such as laminin, NCAM (Neural-Cell Adhesion Molecule) and the stress-inducible protein 1 (STI1). PrPC association with these proteins in neurons mediates adhesion, differentiation and protection against programmed cell death. Herein, we used an aversively motivated learning paradigm in rats to investigate whether STI1 interaction with PrPC affects short-term memory (STM) formation and long-term memory (LTM) consolidation. Blockage of PrPC-STI1 interaction with intra-hippocampal infusion of antibodies against PrPC or STI1 immediately after training impaired both STM and LTM. Furthermore, infusion of PrPC peptide 106-126, which competes for PrPC-STI1 interaction, also inhibited both forms of memory. Remarkably, STII peptide 230-245, which includes the PrPC binding site, had a potent enhancing effect on memory performance, which could be blocked by co-treatment with the competitive PrPC peptide 106-126. Taken together, these results demonstrate that PrPC-STI1 interaction modulates both STM and LTM and suggests a potential use of STI1 peptide 230-245 as a pharmacological agent. (c) 2007 Elsevier Inc. All rights reserved.
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