Coppens Jessica, Bentea Eduard, Bayliss Jacqueline A, Demuyser Thomas, Walrave Laura, Albertini Giulia, Van Liefferinge Joeri, Deneyer Lauren, Aourz Najat, Van Eeckhaut Ann, Portelli Jeanelle, Andrews Zane B, Massie Ann, De Bundel Dimitri, Smolders Ilse
Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium.
Research Group Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium.
Int J Mol Sci. 2017 Mar 4;18(3):558. doi: 10.3390/ijms18030558.
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by a loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Caloric restriction (CR) has been shown to exert ghrelin-dependent neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-based animal model for PD. We here investigated whether CR is neuroprotective in the lactacystin (LAC) mouse model for PD, in which proteasome disruption leads to the destruction of the DA neurons of the SNc, and whether this effect is mediated via the ghrelin receptor. Adult male ghrelin receptor wildtype (WT) and knockout (KO) mice were maintained on an ad libitum (AL) diet or on a 30% CR regimen. After 3 weeks, LAC was injected unilaterally into the SNc, and the degree of DA neuron degeneration was evaluated 1 week later. In AL mice, LAC injection significanty reduced the number of DA neurons and striatal DA concentrations. CR protected against DA neuron degeneration following LAC injection. However, no differences were observed between ghrelin receptor WT and KO mice. These results indicate that CR can protect the nigral DA neurons from toxicity related to proteasome disruption; however, the ghrelin receptor is not involved in this effect.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质致密部（SNc）中的多巴胺（DA）神经元丧失。在基于1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的帕金森病动物模型中，热量限制（CR）已被证明具有依赖于胃饥饿素的神经保护作用。我们在此研究了CR在蛋白酶体抑制剂（LAC）诱导的帕金森病小鼠模型中是否具有神经保护作用，在该模型中蛋白酶体破坏导致SNc中的DA神经元受损，以及这种作用是否通过胃饥饿素受体介导。成年雄性胃饥饿素受体野生型（WT）和敲除（KO）小鼠分别自由进食（AL）或接受30%的热量限制方案。3周后，将LAC单侧注射到SNc中，1周后评估DA神经元的退化程度。在自由进食的小鼠中，注射LAC显著减少了DA神经元的数量和纹状体DA浓度。热量限制可防止LAC注射后DA神经元的退化。然而，在胃饥饿素受体野生型小鼠和敲除小鼠之间未观察到差异。这些结果表明，热量限制可以保护黑质DA神经元免受与蛋白酶体破坏相关的毒性作用；然而，胃饥饿素受体不参与这种作用。
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