The activation of NF-KB is required for the long term memory consolidation in the passive avoidance learning mice.

FREUDENTHAL R, BOCCIA MM, ACOSTA GB, BLAKE, MG, MERLO E, BARATTI CM, ROMANO A

Mar del Plata, 16-20 de Noviembre de 2004.

Congreso; 1er Congreso Conjunto de Sociedades Biomédicas.; 2004

SAFE, SAN, SAB, SAI, SAIC, SAB, SAF

Although is generally accepted that memory consolidation requires gene expression, only few transcription factors (TFs) were clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of Rel/ NF-kB family of TFs in memory and neural plasticity. Here we found that icv post-training administration of sulfasalazine, an inhibitor of NF-kB, impairs long term memory in the one-trial stepthrough inhibitory avoidance paradigm in CF-1 mice. Furthermore, we employed another independent strategy to inhibit NF-kB in the mouse brain, administering a double stranded DNA oligonucleotide containing the NF-kB consensus sequence (kBdecoy). The icv injection of 60 ug of kB decoy 2 h before training induced amnesia, while 60 ug of double stranded DNA oligonucleotides with one base mutation in the consensus sequence (mut-kB-decoy) did not affected long-term memory. NFkB was inhibited in hippocampus 2 h after icv injection of 60 ug of kB-decoy, but no inhibition was found 2 h after mut-kB-decoy injection, estimated by electrophoretic mobility shift assay (EMSA). A temporal course of hippocampal NF-kB activity after training was determining by EMSA. Unexpectedly, an inhibition of NF-kB was found 15 min after training session in the shocked trained group but not in the unshoked-control group. Forty five min after training, hippocampal NF-kB was activated in both shocked and unshocked groups, returning to basal levels 2 hs after training. Based on the latter result, we propose that the activation of NF-kB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitutes the conditioned stimulus representation. The results presented here provide the first evidence supporting that NF-kB activity is regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.