title: The effect of neuronal conditional knock-out of peroxisome proliferator-activated receptors in the MPTP mouse model of Parkinson's disease.
abstract: Activation of peroxisome proliferator-activated receptors (PPARs), namely PPARγ and PPARδ, has been shown to provide neuroprotection in a number of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease (PD). The observed neuroprotective effects in experimental models of PD have been linked to anti-oxidant and anti-inflammatory actions. This study aimed to analyze the full influence of these receptors in neuroprotection by generating a nerve cell-specific conditional knock-out of these receptors and subjecting these genetically modified mice to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to model dopaminergic degeneration. Mice null for both receptors show the lowest levels of tyrosine hydroxylase (TH)-positive cell bodies following MPTP administration. Presence of one or both these receptors show a trend toward protection against this degeneration, as higher dopaminergic cell immunoreactivity and striatal monoamine levels are evident. These data supplement recent studies that have elected to use agonists of the receptors to regulate immune responses. The results place further importance on the activation of PPARs and the neuroprotective roles these have in inflammatory processes linked to neurodegenerative processes.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: R B
authors.initials: RB
authors.lastname: Mounsey
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom; Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: H L
authors.initials: HL
authors.lastname: Martin
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, CA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Nelson
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, CA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom. Electronic address: p.teismann@abdn.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Teismann
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D047494:PPAR delta; D047495:PPAR gamma; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: MPTP; Parkinson’s disease; neurodegeneration; peroxisome proliferator-activated receptor