Role of α-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation

Lasaga, Mercedes; Debéljuk, Luciano; Durand, Daniela Elizabeth; Scimonelli, Teresa Nieves; Caruso, Carla Mariana

doi:10.1016/j.peptides.2008.06.009

Cited by 61 publications

(42 citation statements)

References 129 publications

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“…As MC3R and MC4R expression in the CNS is high, they are more likely responsible for central melanocortin actions. MC4R involvement in anti-inflammatory actions of melanocortins in the brain has been suggested (Lasaga et al 2008). Central administration of a-MSH markedly reduces induction of hypothalamic iNOS and Cox2 gene expression in rats injected with LPS, an effect prevented by central administration of the selective MC4R antagonist HS024 (Caruso et al 2004), indicating for the first time a role for MC4R in inflammation.…”

Section: Mc4r and Inflammationmentioning

confidence: 99%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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Astrocytes exert a wide variety of functions with paramount importance in brain physiology. After injury or infection, astrocytes become reactive and they respond by producing a variety of inflammatory mediators that help maintain brain homeostasis. Loss of astrocyte functions as well as their excessive activation can contribute to disease processes; thus, it is important to modulate reactive astrocyte response. Melanocortins are peptides with well-recognized anti-inflammatory and neuroprotective activity. Although melanocortin efficacy was shown in systemic models of inflammatory disease, mechanisms involved in their effects have not yet been fully elucidated. Central anti-inflammatory effects of melanocortins and their mechanisms are even less well known, and, in particular, the effects of melanocortins in glial cells are poorly understood. Of the five known melanocortin receptors (MCRs), only subtype 4 is present in astrocytes. MC4R has been shown to mediate melanocortin effects on energy homeostasis, reproduction, inflammation, and neuroprotection and, recently, to modulate astrocyte functions. In this review, we will describe MC4R involvement in anti-inflammatory, anorexigenic, and anti-apoptotic effects of melanocortins in the brain. We will highlight MC4R action in astrocytes and discuss their possible mechanisms of action. Melanocortin effects on astrocytes provide a new means of treating inflammation, obesity, and neurodegeneration, making them attractive targets for therapeutic interventions in the CNS.

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Section: Mc4r and Inflammationmentioning

confidence: 99%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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“…The melanocortin receptors, specifically MC4R have been found in brain regions both within and outside of the hypothalamus, implicating areas other than the ARC as potential targets for energy homeostatic regulation by melanocortins (Lasaga et al 2008). Although MC4R mRNA localization to the reward center in the ventral tegmental area (VTA) has been identified in some studies (Alvaro et al 1996, Leriche et al 2007, this has not been confirmed in another study (Kishi et al 2003).…”

Section: Introductionmentioning

confidence: 98%

POMC overexpression in the ventral tegmental area ameliorates dietary obesity

Andino

Ryder

Shapiro

et al. 2011

Journal of Endocrinology

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The activation of proopiomelanocortin (POMC) neurons in different regions of the brain, including the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the solitary tract curtails feeding and attenuates body weight. In this study, we compared the effects of delivery of a recombinant adeno-associated viral (rAAV) construct encoding POMC to the ARC with delivery to the ventral tegmental area (VTA). F344!Brown Norway rats were high-fat (HF) fed for 14 days after which self-complementary rAAV constructs expressing either green fluorescent protein or the POMC gene were injected using coordinates targeting either the VTA or the ARC. Corresponding increased POMC levels were found at the predicted injection sites and subsequent a-melanocyte-stimulating hormone levels were observed.Food intake and body weight were measured for 4 months. Although caloric intake was unaltered by POMC overexpression, weight gain was tempered with POMC overexpression in either the VTA or the ARC compared with controls. There were parallel decreases in adipose tissue reserves. In addition, levels of oxygen consumption and brown adipose tissue uncoupling protein 1 were significantly elevated with POMC treatment in the VTA. Interestingly, tyrosine hydroxylase levels were increased in both the ARC and VTA with POMC overexpression in either the ARC or the VTA. In conclusion, these data indicate a role for POMC overexpression within the VTA reward center to combat HF-induced obesity.

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“…Therefore, considering that an anti-inflammatory role for α-MSH has been demonstrated in both periphery (Hiltz and Lipton, 1989) and central nervous system (Lasaga et al, 2008;Muceniece and Dambrova, 2010), we hypothesized that α-MSH would probably be more effective in an experimental model of status epilepticus that depends on peripheral and central inflammation, the pilocarpine model. However, the systemic administration of α-MSH, at doses recognized to decrease peripheral and central inflammatory markers (Ichiyama et al, 1999;Rajora et al, 1997), did not attenuate pilocarpine-induced seizures, further suggesting a lack of anticonvulsant effect of α-MSH.…”

Section: Discussionmentioning

confidence: 99%