PMID- 28273852 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 3 DP - 2017 Mar 4 TI - Caloric Restriction Protects against Lactacystin-Induced Degeneration of Dopamine Neurons Independent of the Ghrelin Receptor. LID - 10.3390/ijms18030558 [doi] LID - 558 AB - 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. FAU - Coppens, Jessica AU - Coppens J AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. jescoppe@vub.ac.be. FAU - Bentea, Eduard AU - Bentea E AD - 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. FAU - Bayliss, Jacqueline A AU - Bayliss JA AD - Department of Physiology, School of Biomedical and Psychological Sciences, Monash University, Clayton, Melbourne 3800, Australia. jacqueline.bayliss@monash.edu. FAU - Demuyser, Thomas AU - Demuyser T AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. thomas.demuyser@vub.ac.be. FAU - Walrave, Laura AU - Walrave L AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. laura.walrave@vub.ac.be. FAU - Albertini, Giulia AU - Albertini G AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. giulia.albertini@vub.ac.be. FAU - Van Liefferinge, Joeri AU - Van Liefferinge J AD - 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. FAU - Deneyer, Lauren AU - Deneyer L AD - 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. FAU - Aourz, Najat AU - Aourz N AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. najat.aourz@vub.ac.be. FAU - Van Eeckhaut, Ann AU - Van Eeckhaut A AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. aveeckha@vub.ac.be. FAU - Portelli, Jeanelle AU - Portelli J AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. jeanelle.portelli@vub.ac.be. FAU - Andrews, Zane B AU - Andrews ZB AD - Department of Physiology, School of Biomedical and Psychological Sciences, Monash University, Clayton, Melbourne 3800, Australia. zane.andrews@monash.edu. FAU - Massie, Ann AU - Massie A AD - 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. FAU - De Bundel, Dimitri AU - De Bundel D AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ddebunde@vub.ac.be. FAU - Smolders, Ilse AU - Smolders I AD - Research Group Experimental Pharmacology (EFAR/FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium. ilse.smolders@vub.ac.be. LA - eng PT - Journal Article DEP - 20170304 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Neuroprotective Agents) RN - 0 (Receptors, Ghrelin) RN - 133343-34-7 (lactacystin) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/administration & dosage/*analogs & derivatives/pharmacology MH - Age Factors MH - Animals MH - *Caloric Restriction MH - Cell Count MH - Dopaminergic Neurons/*drug effects/*metabolism MH - Male MH - Mice MH - Mice, Knockout MH - *Neuroprotective Agents MH - Receptors, Ghrelin/genetics/*metabolism MH - Substantia Nigra/drug effects/metabolism/pathology PMC - PMC5372574 OTO - NOTNLM OT - Parkinson's disease OT - caloric restriction OT - ghrelin receptor OT - lactacystin COIS- The authors declare no conflict of interest. EDAT- 2017/03/10 06:00 MHDA- 2017/04/30 06:00 PMCR- 2017/03/01 CRDT- 2017/03/10 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/02/14 00:00 [revised] PHST- 2017/02/20 00:00 [accepted] PHST- 2017/03/10 06:00 [entrez] PHST- 2017/03/10 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2017/03/01 00:00 [pmc-release] AID - ijms18030558 [pii] AID - ijms-18-00558 [pii] AID - 10.3390/ijms18030558 [doi] PST - epublish SO - Int J Mol Sci. 2017 Mar 4;18(3):558. doi: 10.3390/ijms18030558.