title: Caloric Restriction Protects against Lactacystin-Induced Degeneration of Dopamine Neurons Independent of the Ghrelin Receptor.
abstract: 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.
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. jescoppe@vub.ac.be.
authors.forename: Jessica
authors.initials: J
authors.lastname: Coppens
authors.affiliation: Research Group Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ebentea@vub.ac.be.
authors.forename: Eduard
authors.initials: E
authors.lastname: Bentea
authors.affiliation: Department of Physiology, School of Biomedical and Psychological Sciences, Monash University, Clayton, Melbourne 3800, Australia. jacqueline.bayliss@monash.edu.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Bayliss
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. thomas.demuyser@vub.ac.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: Demuyser
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. laura.walrave@vub.ac.be.
authors.forename: Laura
authors.initials: L
authors.lastname: Walrave
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. giulia.albertini@vub.ac.be.
authors.forename: Giulia
authors.initials: G
authors.lastname: Albertini
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. joeri.van.liefferinge@vub.ac.be.
authors.forename: Joeri
authors.initials: J
authors.lastname: Van Liefferinge
authors.affiliation: Research Group Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. lauren.deneyer@vub.ac.be.
authors.forename: Lauren
authors.initials: L
authors.lastname: Deneyer
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. najat.aourz@vub.ac.be.
authors.forename: Najat
authors.initials: N
authors.lastname: Aourz
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. aveeckha@vub.ac.be.
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. jeanelle.portelli@vub.ac.be.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Portelli
authors.affiliation: Department of Physiology, School of Biomedical and Psychological Sciences, Monash University, Clayton, Melbourne 3800, Australia. zane.andrews@monash.edu.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Research Group Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ann.massie@vub.ac.be.
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ddebunde@vub.ac.be.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.affiliation: Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ilse.smolders@vub.ac.be.
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D031204:Caloric Restriction; D002452:Cell Count; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D054440:Receptors, Ghrelin; C067713:lactacystin; D000111:Acetylcysteine
keywords: Parkinson’s disease; caloric restriction; ghrelin receptor; lactacystin