Mecanismos moleculares involucrados en el efecto de IL-1beta sobre la consolidación de la memoria y su modulación por alfa-MSH

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

Huerta Grande

Congreso; 1º reunión conjunta Taller de Neurociencias - SAN; 2009

We previously reported that administration of IL-1beta in dorsal hippocampus impairs 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 0.05 ug) did not reverse this effect. The inhibitory effect of IL-1beta on memory consolidation was not reversed 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 (100uM) 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.