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

作者：Kalonia Harikesh; Kumar Puneet; Kumar Anil^*

来源：Pharmacology Biochemistry and Behavior, 2010, 96(2): 115-124.

DOI：10.1016/j.pbb.2010.04.018

• Antioxidant
• Mitochondrial dysfunction
• Pioglitazone
• Neurotoxicity
• Oxidative stress

Emerging evidence indicates that PPAR Gamma 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 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 TNE-alpha level as compared to sham treated animals. Pioglitazone (10, 20 and 40 mg/kg, p.o.) treatment significantly improved body weight and motor functions, oxidative defense. Further, pioglitazone treatment restored mitochondrial enzyme complex activity as well as TNE-alpha level as compared to QUIN treated group. While Bisphenol A diglycidyl ether (BADGE) (15 mg/kg), PPAR Gamma antagonist significantly reversed the protective effect of the pioglitazone (40 mg/kg) in the QUIN treated animals. Further, pioglitazone treatment significantly attenuated the striatal lesion volume in QUIN treated animals, suggesting a role for the PPAR Gamma pathway in QUIN induced neurotoxicity. Altogether, this evidence indicates that PPAR Gamma activation by pioglitazone attenuated QUIN induced neurotoxicity in animals and which could be an important therapeutic avenue to ameliorate Huntington like symptoms.

• 出版日期2010-8