Astrocytes: new targets of melanocortin 4 receptor actions

Abstract

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.

Structural changes in thestrial blood–labyrinth barrier of aged C57BL/6 mice

“…We previously found that PVM/Ms are activated in animals exposed to loud sound or induced to inflammation(Zhang et al 2013b; Zhang et al 2013a). Similar astrocyte activation is seen in brain ischemic diseases(Caruso et al 2013). Is PVM/M “activation” also elicited by hypoxia?…”

Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice

“…Glucose is transported from the blood through endothelium cells by astrocytes (Simpson et al, 2007), which actively modulate neuronal homeostasis and metabolism in the central nervous system (Caruso et al, 2013). Astrocytes extend processes terminating in end feet that encapsulate capillaries to control the blood-brain barrier and molecular exchange between the blood and brain parenchyma (Abbott et al, 2006).…”

Novel Variants in theMC4RandLEPRGenes among Severely Obese Children from the Iberian Population

“…It is thought to explain 2-6% of extremely obese childhood and adolescent cases (Farooqi et al, 2003;Hinney et al, 2003Hinney et al, , 2006Santini et al, 2004;Wang & Tao, 2011). The MC4R is a membrane-bound G-protein-coupled receptor that activates adenylate cyclase; in response to the α-melanocyte-stimulating hormone (α-MSH), MC4R induces production of cAMP (Stutzmann et al, 2008;Caruso et al, 2013). The expression of MC4R is restricted to the brain, where it is found in hypothalamic nuclei involved in food intake regulation (Mountjoy et al, 1994).…”