title: Molecular mechanisms involved in interleukin 1-beta (IL-1β)-induced memory impairment. Modulation by alpha-melanocyte-stimulating hormone (α-MSH).
abstract: Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1β (IL-1β) influences the consolidation of hippocampus-dependent memories. We previously reported that administration of IL-1β in dorsal hippocampus impaired contextual fear memory consolidation. Different mechanisms have been implicated in the action of IL-1β 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-1β induced a significant increase in p38 phosphorylation after contextual fear conditioning. Also, treatment with SB203580, an inhibitor of p38, reversed impairment induced by IL-1β on conditioned fear behavior, indicating that this MAPK would be involved in the effect of the cytokine. We also showed that IL-1β 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-1β-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-1β on contextual fear memory. Furthermore, we demonstrated that IL-1β produced a temporal delay in ERK phosphorylation and that DCS administration reversed this effect. We also observed that intrahippocampal injection of IL-1β decreased BDNF expression after contextual fear conditioning. We previously demonstrated that α-MSH reversed the detrimental effect of IL-1β on memory consolidation. The present results demonstrate that α-MSH administration did not modify the decrease in glutamate release induced by IL-1β. However, intrahippocampal injection of α-MSH prevented the effect on ERK phosphorylation and BDNF expression induced by IL-1β after contextual fear conditioning. Therefore, in the present study we determine possible molecular mechanisms involved in the impairment induced by IL-1β on fear memory consolidation. We also established how this effect could be modulated by α-MSH.
authors: IFEC-CONICET, Depto. Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
authors: P
authors: P
authors: Gonzalez
authors: I
authors: I
authors: Machado
authors: A
authors: A
authors: Vilcaes
authors: C
authors: C
authors: Caruso
authors: G A
authors: GA
authors: Roth
authors: H
authors: H
authors: Schiöth
authors: M
authors: M
authors: Lasaga
authors: T
authors: T
authors: Scimonelli
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005239:Fear / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism*; D017208:Rats, Wistar; D000521:alpha-MSH / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D018698:Glutamic Acid; D000521:alpha-MSH; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: BDNF; ERK; Glutamate release; IL-1β; Memory consolidation; p38; α-MSH