The effect of neuronal conditional knock-out of peroxisome proliferator-activated receptors in the MPTP mouse model of Parkinson's disease

R. B. Mounsey, H. L. Martin, M. C. Nelson, R. M. Evans, P. Teismann

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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.
Original languageEnglish
Pages (from-to)576-584
Number of pages9
Early online date29 May 2015
Publication statusPublished - 6 Aug 2015

Bibliographical note

This study was supported by Parkinson’s Disease Foundation (IRGP 09-11 (P.T.)), the Royal Society (2006/R1 (P.T.)), the Wellcome Trust (WT080782MF (P.T.)), the Biotechnology and Biological Sciences Research Council (P.T. and H.L.M.), the National Institutes of Health (DK057978) (R.M.E.), and by grants from the Leona M. and Harry B. Helmsley Charitable Trust (R.M.E.), the Glenn Foundation for Medical Research (R.M.E.), and the Ellison Medical Foundation (R.M.E.). R.M.E. is an investigator at the Howard Hughes Medical Institute and March of Dimes Chair in Molecular and Developmental Biology at the Salk Institute. The authors would like to thank Lynne J. Hocking, University of Aberdeen, for her assistance with the statistics. We are grateful to the staff of the Medical Research Facility for their help with the animal care and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment.


  • Parkinson’s disease
  • MPTP
  • neurodegeneration
  • peroxisome proliferator-activated receptor


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