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The interaction between prion protein and laminin modulates memory consolidation
Author(s) -
Coitinho Adriana S.,
Freitas Adriana R. O.,
Lopes Marilene H.,
Hajj Glaucia N. M.,
Roesler Rafael,
Walz Roger,
Rossato Janine I.,
Cammarota Martin,
Izquierdo Ivan,
Martins Vilma R.,
Brentani Ricardo R.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05156.x
Subject(s) - memory consolidation , peptide , inhibitory postsynaptic potential , hippocampal formation , chemistry , microbiology and biotechnology , kinase , extracellular , signal transduction , receptor , protein kinase a , biology , biochemistry , neuroscience , hippocampus
Cellular prion protein (PrP c ) has a pivotal role in prion diseases. PrP c is a specific receptor for laminin (LN) γ1 peptide and several lines of evidence indicate that it is also involved in neural plasticity. Here we investigated whether the interaction between PrP c and LN plays a role in rat memory formation. We found that post‐training intrahippocampal infusion of PrP c ‐derived peptides that contain the LN binding site ( and ) or of anti‐PrP c or anti‐LN antibodies that inhibit PrP c –LN interaction impaired inhibitory avoidance memory retention. The amnesic effect of anti‐PrP c antibodies and peptide was reversed by co‐infusion of a LN γ1 chain‐derived peptide containing the PrP c ‐binding site, suggesting that PrP c –LN interaction is indeed crucial for memory consolidation. In addition, peptide and anti‐PrP c or anti‐LN antibodies also inhibited the activation of hippocampal cAMP‐dependent protein kinase A (PKA) and extracellular regulated kinase (ERK1/2), two kinases that mediate the up‐regulation of signaling pathways needed for consolidation of inhibitory avoidance memory. Our findings show that, through its interaction with LN, hippocampal PrP c plays a critical role in memory processing and suggest that this role is mediated by activation of both PKA and ERK1/2 signaling pathways.