Molecular mechanisms involved in interleukin 1-beta (IL-1b)-induced memory impairment. Modulation by alpha-melanocyte-stimulating hormone (alpha-MSH)

GONZALEZ P.; MACHADO I.; VILCAES A.; CARUSO C.; ROTH G.A. ; SCHIOTH H.B.; LASAGA M.; SCIMONELLI T.

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2013 vol. 34 p. 141 - 150

0889-1591

Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly,interleukin-1b (IL-1b) influences the consolidation of hippocampus-dependent memories. We previously reported that administration of IL-1b in dorsal hippocampus impaired contextual fear memory consolidation. Different mechanisms have been implicated in the action of IL-1b on long-term potentiation (LTP), but the processes by which this inhibition occurs in vivo remain to be elucidated. We herein report that intrahippocampal injection of IL-1b induced a significant increase in p38 phosphorylation after contextual fear conditioning. Also, treatment with SB203580, an inhibitor of p38, reversed impairment induced by IL-1b on conditioned fear behavior, indicating that this MAPK would be involved in the effect of the cytokine.We also showed that IL-1b administration produced a decrease in glutamate release from dorsal hippocampus synaptosomes and that treatment with SB203580 partially reversed this effect. Our results indicated that IL-1b-induced impairment in memory consolidation could be mediated by a decrease in glutamate release. This hypothesis is sustained by the fact that treatment with D-cycloserine (DCS), a partial agonist of the NMDA receptor, reversed the effect of IL-1b on contextual fear memory. Furthermore, we demonstrated that IL-1b produced a temporal delay in ERK phosphorylation and that DCS administration reversed this effect. We also observed that intrahippocampal injection of IL-1b decreased BDNF expression after contextual fear conditioning. We previously demonstrated that alpha- MSH reversed the detrimental effect of IL-1b on memory consolidation. The present results demonstrate that alpha-MSH administration did not modify the decrease in glutamate release induced by IL-1b. However,intrahippocampal injection of alpha-MSH prevented the effect on ERK phosphorylation and BDNF expression induced by IL-1b after contextual fear conditioning. Therefore, in the present study we determine possible molecular mechanisms involved in the impairment induced by IL-1b on fear memory consolidation. We also established how this effect could be modulated by alpha-MSH.