Coitinho Adriana S, Lopes Marilene H, Hajj Glaucia N M, Rossato Janine I, Freitas Adriana R, Castro Cibele C, Cammarota Martin, Brentani Ricardo R, Izquierdo Ivan, Martins Vilma R
Centro Universitário Feevale, Instituto de Ciências da Saúde, RS 239, 2755, 93352-000, Novo Hamburgo, RS, Brazil.
Neurobiol Dis. 2007 Apr;26(1):282-90. doi: 10.1016/j.nbd.2007.01.005. Epub 2007 Jan 25.
Cellular prion protein (PrP(C)) 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). PrP(C) 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 PrP(C) affects short-term memory (STM) formation and long-term memory (LTM) consolidation. Blockage of PrP(C)-STI1 interaction with intra-hippocampal infusion of antibodies against PrP(C) or STI1 immediately after training impaired both STM and LTM. Furthermore, infusion of PrP(C) peptide 106-126, which competes for PrP(C)-STI1 interaction, also inhibited both forms of memory. Remarkably, STI1 peptide 230-245, which includes the PrP(C) binding site, had a potent enhancing effect on memory performance, which could be blocked by co-treatment with the competitive PrP(C) peptide 106-126. Taken together, these results demonstrate that PrP(C)-STI1 interaction modulates both STM and LTM and suggests a potential use of ST11 peptide 230-245 as a pharmacological agent.
细胞朊蛋白（PrP(C)）是一种细胞表面糖蛋白，可与多种配体相互作用，如层粘连蛋白、神经细胞黏附分子（NCAM）和应激诱导蛋白1（STI1）。PrP(C)在神经元中与这些蛋白质的结合介导了黏附、分化以及对程序性细胞死亡的保护作用。在此，我们利用大鼠的厌恶性动机学习范式，研究STI1与PrP(C)的相互作用是否会影响短期记忆（STM）的形成和长期记忆（LTM）的巩固。训练后立即向海马内注射抗PrP(C)或STI1抗体以阻断PrP(C)-STI1的相互作用，会损害STM和LTM。此外，注入竞争PrP(C)-STI1相互作用的PrP(C)肽106-126，也会抑制这两种记忆形式。值得注意的是，包含PrP(C)结合位点的STI1肽230-245对记忆表现有强大的增强作用，而与竞争性PrP(C)肽106-126共同处理可阻断这种作用。综上所述，这些结果表明PrP(C)-STI1相互作用调节STM和LTM，并提示ST11肽230-245作为一种药物制剂的潜在用途。
