Modulation of BDNF expression by MC4 receptor activation in rat astrocytes.

CARUSO CARLA; CARNIGLIA LILA; DURAND DANIELA; LASAGA MERCEDES

Huerta Grande, Córdoba

Congreso; Segunda Reunión Conjunta de la Sociedad Argentina de Neurociencias y el Taller Argentino de Neurociencias; 2010

SAN

Melanocortins (ACTH, alpha-, beta- and gamma-MSH) are potent anti-inflammatory neuropeptides. Melanocortin 4 receptor (MC4R) is the only MCR expressed in astrocytes and mediates anti-inflammatory action of melanocortins. Our previous results showed that alpha-MSH, through MC4R, increases CREB activation in astrocytes. Since anti-inflammatory effects could be therapeutical, we studied the mechanisms involved in MC4R activation in cultured rat astrocytes. Since MCRs are G protein-coupled receptors we determined the intracellular levels of cAMP in astrocytes after 20 min of stimulation. In a dose response curve we found that alpha-MSH 1uM elicited the highest increase in intracellular cAMP levels. This effect was blocked by HS024, a MC4R selective antagonist which per se decreased cAMP production. On the other hand, the inflammatory stimulus lipopolysaccharide and interferon-gamma (LPS+IFN-gamma) decreased cAMP levels but co-incubation with alpha-MSH reverted this effect. In addition, treatment with 0.1, 1, and 10 uM NDP-MSH (an alpha-MSH analogue) increased brain-derived neurotrophic factor (BDNF) mRNA levels at 1 or 3 h (p0.05). At 24 h mRNA levels returned to basal values. However, NDP-MSH significantly increased protein levels of BDNF at 24 h (p0.05). In summary, MC4Rs are functional receptors that increase BDNF expression in astrocytes, suggesting that BDNF could be a mediator of MC4R-mediated effects.