IL-1ß reduces GluA1 phosphorylation and its surface expression during memory reconsolidation and α-melanocyte-stimulating hormone can modulate these effects.

Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1ß (IL-1ß) influences hippocampus-dependent memories. We previously reported that administration of IL-1ß in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). Our results also demonstrated that IL-1ß produced a significant decrease in glutamate release from dorsal hippocampus synaptosomes after reactivation of the fear memory. Therefore, we investigated whether IL-1ß administration can affect GluA1 AMPA subunit phosphorylation, surface expression, and total expression during reconsolidation of a contextual fear memory. Also, we studied the modulatory effect of α-MSH. We found that IL-1ß reduced phosphorylation of this subunit at Serine 831 and Serine 845 60 min after contextual fear memory reactivation. The intrahippocampal administration of IL-1ß after memory reactivation also induced a decrease in surface expression and total expression of GluA1. α-MSH prevented the effect of IL-1ß on GluA1 phosphorylation in Serine 845, but not in Serine 831. Moreover, treatment with α-MSH also prevented the effect of the cytokine on GluA1 surface and total expression after memory reactivation. Our results demonstrated that IL-1ß regulates phosphorylation of GluA1 and may thus play an important role in modulation of AMPAR function and synaptic plasticity in the brain. These findings further illustrate the importance of IL-1ß in cognition processes dependent on the hippocampus, and also reinforced the fact that α-MSH can reverse IL-1ß effects on memory reconsolidation.

Interleukin-1ß-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and α-melanocyte-stimulating hormone prevented these effects.

The immune system is an important modulator of learning, memory and neural plasticity. Interleukin 1ß (IL-1ß), a pro-inflammatory cytokine, significantly affects several cognitive processes. Previous studies by our group have demonstrated that intrahippocampal administration of IL-1ß impairs reconsolidation of contextual fear memory. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). The mechanisms underlying the effect of IL-1ß on memory reconsolidation have not yet been established. Therefore, we examined the effect of IL-1ß on glutamate release, ERK phosphorylation and the activation of the transcription factor zinc finger- 268 (zif268) during reconsolidation. Our results demonstrated that IL-1ß induced a significant decrease of glutamate release after reactivation of the fear memory and this effect was related to calcium concentration in hippocampal synaptosomes. IL-1ß also reduced ERK phosphorylation and zif268 expression in the hippocampus. Central administration of α-MSH prevented the decrease in glutamate release, ERK phosphorylation and zif268 expression induced by IL-1ß. Our results establish possible mechanisms involved in the detrimental effect of IL-1ß on memory reconsolidation and also indicate that α-MSH may exert a beneficial modulatory role in preventing IL-1ß effects.

α-Melanocyte-stimulating hormone (α-MSH) reverses impairment of memory reconsolidation induced by interleukin-1 beta (IL-1 beta) hippocampal infusions.

Interleukin-1 beta (IL-1ß) significantly influences cognitive processes. Treatments which raise the level of IL-1ß in the brain impair memory consolidation in contextual fear conditioning. However, the effect of IL-1ß on memory reconsolidation has not yet been established. The melanocortin α-melanocyte-stimulating hormone (α-MSH) exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, of which MC3R and MC4R are predominant in the central nervous system. The present experiments show that the injection of IL-1ß (5 ng/0.25 µl) in dorsal hippocampus up to 30 min after re-exposition to the context decreases freezing during the contextual fear test. Impairment of memory reconsolidation was reversed by treatment with α-MSH (0.05 µg/0.25 µl). Administration of the MC4 receptor antagonist HS014 (0.5 µg/0.25 µl) blocked the effect of α-MSH. These results suggest that IL-1ß may influence memory reconsolidation and that activation of central MC4R could lead to improve cognitive performance.