Molecular mechanisms involved in the effect of IL-1beta on memory consolidation

GONZALEZ PATRICIA; CARNIGLIA LILA; MACHADO IVANA; VILCÁES ALEJANDRO; LASAGA MERCEDES; SCIMONELLI TERESA

Congreso; Society for Neurosciences 40th Annual Meeting.; 2010

The effects of cytokines on cognitive processes have been extensively studied. Particularly, IL-1b significantly influences consolidation of memories that depend on hippocampus. Concordantly, we previously reported that administration of IL-1b in dorsal hippocampus impaired the consolidation of a contextual fear memory and that treatment with a-MSH blocked this effect (1). However, the mechanisms involved in the effect of IL-1b on memory consolidation have not been established yet. It has been demonstrated that activation of p38 and Jun-kinase are involved in the inhibitory effect of LPS and IL-1b on long term potentiation in vitro and that this effect was attenuated by an NF-kB inhibitor. Here we show that intrahippocampal injection of IL-1b after training in a contextual fear paradigm induced a non-significant increase in p38 phosphorylation, indicating that this MAPK wouldn’t be involved in the effect of IL-1b.  Besides, western blot analysis demonstrated that IL-1b induced a significant increase in nuclear NF-kB in dorsal hippocampus. We also observed that intrahippocampal injection of IL-1b after training induced a decreased in the glutamate release from dorsal hippocampus synaptosomes. The results are consistent with the idea that IL-1b-induced impairment in memory consolidation could be mediated by a decreased in glutamate release. On the other hand, a-MSH administration did not modify NfkB activation and glutamate levels induced by IL-1b. Considering that a-MSH reversed the effect of IL-1b on memory consolidation, and that a-MSH administration did not modify the effects of IL-1b on the molecular mechanisms studied, further investigation is required to establish the signalling cascade involved in this modulation.