Molecular mechanisms involved in the effect of IL-1 beta on memory consolidation and their modulation by alpha-MSH

GONZALEZ PATRICIA; MACHADO IVANA ; VILCAES ALDO; CARNIGLIA LILA; LASAGA MERCEDES; SCIMONELLI TERESA

Huerta Grande

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

SAN, Sociedad Argentina de neurociencias

Molecular mechanisms involved in the effect of IL-1beta on memory consolidation and their modulation by alpha-MSH.We previously reported that administration of IL-1 beta in dorsal hippocampus impair the consolidation of a contextual fear memory. Treatment with alpha-MSH blocked this effect. However, the mechanisms involved in the cytokine effect were not establish yet. It has been demonstrated that activation of p38 and Jun-kinase are involved in the inhibitory effect of LPS and IL-1beta on LTP in vitro. Also, this effect was attenuated by a NF-kB inhibitor. The present experiments show that intrahippocampal injection of IL-1beta after training in a contextual fear paradigm induced a decreased in the glutamate release from dorsal hippocampus. alpha-MSH administration (0.05ug) did not reverse this effect. The inhibitory effect of IL-1? on memory consolidation was not reverse by the NF-kB inhibitor SN50 (20ug). However, western blot analysis demonstrated that IL-1beta induce a significant increased in nuclear NF-kB in dorsal hippocampus. Probably, as described before, astrocytes are the source of the increased in NF-kB, and so, this effect was not involved in memory consolidation. Preliminary results show that the inhibition of p38 phosphorylation by SB203580 reduced the effect of IL-1beta on memory consolidation. The results are consistent with the idea that IL-1beta-induced impairment in memory consolidation is mediated by a decreased in glutamate released and p38 MAPK activation in dorsal hippocampus.