title: Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction model in the marmoset without persistent molecular and cellular damage.
abstract: Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. MPTP-induced parkinsonian clinical symptoms increased in severity during exposure, and recovered after MPTP administration was ended. Postmortem analyses, after the recovery period, revealed no alteration of the number and sizes of tyrosine hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands; Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: S K
authors.initials: SK
authors.lastname: Franke
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: van Kesteren
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: J A M
authors.initials: JA
authors.lastname: Wubben
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Hofman
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Paliukhovich
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: R C
authors.initials: RC
authors.lastname: van der Schors
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van Nierop
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands. Electronic address: philippens@bprc.nl.
authors.forename: I H C H M
authors.initials: IH
authors.lastname: Philippens
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002144:Callithrix; D004195:Disease Models, Animal; D018450:Disease Progression; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D020127:Recovery of Function; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Parkinson; behavior; chronic MPTP; marmoset; proteomics; recovery