Melanocortin 4 receptor activation protects striatal neurons and glial cells from 3-nitropropionic acid toxicity

Publication date: Available online 4 December 2018Source: Molecular and Cellular NeuroscienceAuthor(s): Julieta Saba, Lila Carniglia, Delia Ramírez, Juan Turati, Mercedes Imsen, Daniela Durand, Mercedes Lasaga, Carla CarusoAbstractα-Melanocyte stimulating hormone (α-MSH) is a melanocortin which exerts potent anti-inflammatory and anti-apoptotic effects. Melanocortin 4 receptors (MC4R) are abundantly expressed in the brain and we previously demonstrated that [Nle(4), D-Phe(7)]melanocyte-stimulating hormone (NDP-MSH), an α-MSH analogue, increased expression of brain derived-neurotrophic factor (BDNF), and peroxisome proliferator-activated receptor-γ (PPAR-γ). We hypothesized that melanocortins could affect striatal cell survival through BDNF and PPAR-γ. First, we determined the expression of these factors in the striatum. Acute intraperitoneal administration (0.5 mg/kg) of α-MSH increased the levels of BDNF mRNA in rat striatum but not in rat cerebral cortex. Also, protein expression of PPAR-γ and MC4R was increased by acute treatment with α-MSH in striatum but not in cortex. No changes were observed by 48 h treatment. Next, we evaluated melanocortins effect on neuron and glial survival. 3-nitropropionic acid (3-NP), which is known to induce striatal degeneration, was used to induce cell death in the rat striatal cell line ST14A expressing human mutant huntingtin (Q120) or in ST14A cells expressing normal human huntingtin (Q15), in primary cultured astrocytes, and...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research