Interfering with PSD-95 signaling complex affects memory consolidation

SALLES A; BOCCIA MM; MALLON A; KRAWCZYK MC; BARATTI CM; ROMANO A; FREUDENTHAL R

Huerta Grande, Córdoba

Congreso; XXVIII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS & Reunión satélite sobre Neurobiología del Comportamiento: ?NeuroetologÍa y Neurobiología de la Memoria en el cono sur? Un homenaje a Héctor Maldonado; 2013

Sociedad Argentina de Neurociencias

PDZ domains are present in several diverse proteins, including PSD-95 where it wasfirst described. These domains are protein-protein interaction domains that anchormembrane proteins and hold together signaling complexes. NF-kappa B is atranscription factor whose role in memory consolidation was first described by ourlab and widely reported thereafter. Previously in our lab, we observed that NFkappaB was strongly bound to the membranes of synaptosomes. Additionally,consolidation of inhibitory avoidance memories in mice leads to NF-kappa Bactivation at synaptosomes and increased attachment to membrane of thesestructures. Our research suggested the possibility that NF-kappa B interacts withPSD-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 PDZdomains 1 and 2 of PSD-95 with high affinity. We hypothesized AT010 mightmodulate the interaction between NF-kappa B and other proteins. In this work weshow evidence of NF-kappa B and PDS-95 interaction and we show that intrahippocampalinjection of AT010 reversibly interferes with memory consolidation ofthe inhibitory avoidance paradigm in mice Exploratory toxicity studies ofintravenous injections of AT010 showed no signs of toxicity.