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.
(1) Gonzalez PV, Schiöth HB, Lasaga M, Scimonelli TN. Memory impairment induced by IL-1beta is reversed by a-MSH through central melanocortin-4 receptors. Brain Behav Immun. 2009; 23(6):817-22.
