Science and Technology Production
Article
Authorship
CARUSO, CARLA MARIANA
;
L. Carniglia
;
D. Durand
;
P. V. Gonzalez
;
T. Scimonelli
;
M. Lasaga
Date
2012
Publishing House and Editing Place
ELSEVIER IRELAND LTD
Magazine
MOLECULAR AND CELLULAR ENDOCRINOLOGY.,
vol. 348
(pp. 47-54)
ELSEVIER IRELAND LTD
Summary
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SIGEVA
Melanocortin 4 receptors (MC4R) are mainly expressed in the brain. We previously showed that the antiinflammatory action of alpha-melanocyte-stimulating hormone (alpha-MSH) in rat hypothalamus and in cultured astrocytes involved MC4R activation. However, MC4R mechanisms of action remain undetermined. Since brain-derived neurotrophic factor (BDNF) may be mediating MC4R hypothalamic anorexigenic actions, we determined melanocortin effects on BDNF expression in rat cultured astrocytes and certain ...
Melanocortin 4 receptors (MC4R) are mainly expressed in the brain. We previously showed that the antiinflammatory action of alpha-melanocyte-stimulating hormone (alpha-MSH) in rat hypothalamus and in cultured astrocytes involved MC4R activation. However, MC4R mechanisms of action remain undetermined. Since brain-derived neurotrophic factor (BDNF) may be mediating MC4R hypothalamic anorexigenic actions, we determined melanocortin effects on BDNF expression in rat cultured astrocytes and certain mechanisms involved in MC4R signaling. alfa-MSH and its analogue NDP-MSH, induced production of cAMP in astrocytes. This effect was completely blocked by the MC4R antagonist, HS024. We found that NDPMSH increased BDNF mRNA and protein levels in astrocytes. The effect of NDP-MSH on BDNF expression was abolished by the adenylate cyclase inhibitor SQ22536, and decreased by the PKA inhibitor Rp-cAMP. Since melanocortins are immunomodulators, we investigated their actions with bacterial lipopolysaccharide (LPS) and interferon-gama (IFN-gama) stimulus. Although both alpha-MSH and LPS + IFN-gama increased cAMP responding element binding protein (CREB) activation, LPS + IFN-gama did not modify BDNF expression. On the other hand, alpha-MSH did not modify basal or LPS + IFN-gama-induced nuclear factor-kB activation.Our results show for the first time that MC4R activation in astrocytes induces BDNF expression through cAMP-PKA-CREB pathway without involving NF-kB.
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Key Words
MELANOCORTIN 4 RECEPTORAMP CICLICOASTROCITOSBDNF