TY - JOUR
T1 - Molecular mechanisms involved in interleukin 1-beta (IL-1β)-induced memory impairment. Modulation by alpha-melanocyte-stimulating hormone (α-MSH)
AU - Gonzalez, P.
AU - Machado, I.
AU - Vilcaes, A.
AU - Caruso, C.
AU - Roth, G. A.
AU - Schiöth, H.
AU - Lasaga, M.
AU - Scimonelli, T.
N1 - Funding Information:
This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica, University of Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Universidad Nacional de Córdoba, Argentina . HS was supported by the Swedish Research Council . The authors thank Estela Salde for her expert technical assistance.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - BDNF
KW - ERK
KW - Glutamate release
KW - IL-1β
KW - Memory consolidation
KW - P38
KW - α-MSH
UR - http://www.scopus.com/inward/record.url?scp=84885024415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885024415&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2013.08.007
DO - 10.1016/j.bbi.2013.08.007
M3 - Article
C2 - 23968970
AN - SCOPUS:84885024415
SN - 0889-1591
VL - 34
SP - 141
EP - 150
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -