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

First Author  Mounsey RB Year  2015
Journal  Neuroscience Volume  300
Pages  576-84 PubMed ID  26028469
Mgi Jnum  J:224472 Mgi Id  MGI:5662330
Doi  10.1016/j.neuroscience.2015.05.048 Citation  Mounsey RB, et al. (2015) The effect of neuronal conditional knock-out of peroxisome proliferator-activated receptors in the MPTP mouse model of Parkinson's disease. Neuroscience 300:576-84
abstractText  Activation of peroxisome proliferator-activated receptors (PPARs), namely PPARgamma and PPARdelta, 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.
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