PDZ domains 1 and 2 of PSD-95 are necessary for memory c

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

Buenos Aires

Conferencia; FALAN; 2016

FALAN

PDZ domains are present in several diverse proteins,including PSD-95 where it was first described. These areprotein-protein interaction domains that anchor membraneproteins and hold together signalling complexes. PSD-95is a main component of the post-synaptic density and isa member of the MAGUK family of proteins, interactingclosely with NMDA receptors, among others. We used astable, cell-permeable peptide that was designed to bindto the PDZ domains 1 and 2 of PSD-95 with high affinityand we hypothesized that this peptide might modulate theinteraction between PSD-95 and other proteins, affectingmemory consolidation. In this work we show that intrahippocampalinjection of this peptide reversibly interfereswith memory consolidation of the inhibitory avoidanceparadigm in mice. Although previous work has shownthat interfering with the PSD-95 complex with intrathecalinjections of the peptide has an analgesic effect, we showthat it does not impair nociception when injected locally inthe hippocampus. Exploratory toxicity studies of intravenousinjections of the peptide showed no signs of toxicity.