Pioglitazone ameliorates behavioral, biochemical and cellular alterations in quinolinic acid induced neurotoxicity: possible role of peroxisome proliferator activated receptor-Upsilon (PPARUpsilon) in Huntington's disease

Harikesh Kalonia, Puneet Kumar, Anil Kumar
Pharmacology, Biochemistry, and Behavior 2010, 96 (2): 115-24
Emerging evidence indicates that PPARUpsilon activators attenuate neurodegeneration and related complications. Therefore, the present study focused on the neuroprotective potential of pioglitazone against quinolinic acid (QUIN) induced neurotoxicity. Intrastriatal (unilaterally) administration of QUIN significantly altered body weight and motor function (locomotor activity, rotarod and beam walk performance). Further, QUIN treatment significantly caused oxidative damage (increased lipid peroxidation, nitrite concentration and depleted endogenous antioxidant defense enzymes), altered mitochondrial enzyme complex (I, II and IV) activities and TNF-alpha level as compared to sham treated animals. Pioglitazone (10, 20 and 40mg/kg, p.o.) treatment significantly improved body weight and motor functions, oxidative defense. Further, pioglitazone treatment restored mitochondrial enzyme complex activity as well as TNF-alpha level as compared to QUIN treated group. While Bisphenol A diglycidyl ether (BADGE) (15mg/kg), PPARUpsilon antagonist significantly reversed the protective effect of the pioglitazone (40mg/kg) in the QUIN treated animals. Further, pioglitazone treatment significantly attenuated the striatal lesion volume in QUIN treated animals, suggesting a role for the PPARUpsilon pathway in QUIN induced neurotoxicity. Altogether, this evidence indicates that PPARUpsilon activation by pioglitazone attenuated QUIN induced neurotoxicity in animals and which could be an important therapeutic avenue to ameliorate Huntington like symptoms.

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