| First Author | Martin HL | Year | 2013 |
| Journal | Neuroscience | Volume | 240 |
| Pages | 191-203 | PubMed ID | 23500098 |
| Mgi Jnum | J:201361 | Mgi Id | MGI:5513061 |
| Doi | 10.1016/j.neuroscience.2013.02.058 | Citation | Martin HL, et al. (2013) A peroxisome proliferator-activated receptor-delta agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Neuroscience 240:191-203 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR)-gamma and PPARalpha have shown neuroprotective effects in models of Parkinson's disease (PD). The role of the third, more ubiquitous isoform PPARdelta has not been fully explored. This study investigated the role of PPARdelta in PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model the dopaminergic neurodegeneration of PD. In vitro administration of the PPARdelta antagonist GSK0660 (1 muM) increased the detrimental effect of 1-methyl-4-phenylpyridinium iodide (MPP(+)) on cell viability, which was reversed by co-treatment with agonist GW0742 (1 muM). GW0742 alone did not affect MPP(+) toxicity. PPARdelta was expressed in the nucleus of dopaminergic neurons and in astrocytes. Striatal PPARdelta levels were increased (over two-fold) immediately after MPTP treatment (30 mg/kg for 5 consecutive days) compared to saline-treated mice. PPARdelta heterozygous mice were not protected against MPTP toxicity. Intra-striatal infusion of GW0742 (84 mug/day) reduced the MPTP-induced loss of dopaminergic neurons (5036+/-195) when compared to vehicle-infused mice (3953+/-460). These results indicate that agonism of PPARdelta provides protection against MPTP toxicity, in agreement with the effects of other PPAR agonists. |
