Interfering with PSD-95 signalling complex affects memory consolidation.

ANGELES SALLES; MARIANO BOCCIA; ANDREW MALLON; MARIA DEL CARMEN KRAWCZYK; CARLOS MARÍA BARATTI; ARTURO ROMANO; FREUDENTHAL RAMIRO

Huerta Grande

Congreso; XXVIII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2013

SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS

PDZ domains are present in several diverse proteins, including PSD-95 where it was first described. These domains are protein-protein interaction domains that anchor membrane proteins and hold together signaling complexes. NF-kappa B is a transcription factor whose role in memory consolidation was first described by our lab and widely reported thereafter. Previously in our lab, we observed that NF-kappa B was strongly bound to the membranes of synaptosomes. Additionally, consolidation of inhibitory avoidance memories in mice leads to NF-kappa B activation at synaptosomes and increased attachment to membrane of these structures. Our research suggested the possibility that NF-kappa B interacts with PSD-95 and is anchored to the membrane to perform a non-canonical function. AT010 is a stable, cell-permeable peptide that was designed to bind to the PDZ domains 1 and 2 of PSD-95 with high affinity. We hypothesized AT010 might modulate the interaction between NF-kappa B and other proteins. In this work we show that intra-hippocampal injection of AT010 reversibly interferes with memory consolidation of the inhibitory avoidance paradigm in mice Exploratory toxicity studies of intravenous injections of AT010 showed no signs of toxicity.