title: Peroxisome proliferator-activated receptor-α activation attenuates 3-nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms.
abstract: Peroxisome proliferators activated receptor is regarded as potential therapeutic targets to control various neurodegenerative disorders. However, none of the study has elucidated its effect in the treatment of Huntington's disease. We explored whether peroxisome proliferators activated receptor-α agonist may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (3-NP), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-NP (20mg/kg., i.p.) for 4days in rats produced hypolocomotion, muscle incoordination, and cognitive dysfunction. Daily treatment with fenofibrate (100 or 200mg/kg., p.o.), 30min prior to 3-NP administration for a total of 4days, significantly improved the 3-NP induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-NP administration significantly increased oxidative and nitrosative stress (increase lipid peroxidation, protein carbonyls and nitrite level), lactate dehydrogenase activity whereas, decreased the activities of catalase, superoxide dismutase, reduced glutathione, and succinate dehydrogenase. Fenofibrate treatment significantly attenuated oxidative damage, cytokines and improved mitochondrial complexes enzyme activity in brain. In the present study, MK886, a selective inhibitor of peroxisome proliferators activated receptor-α was employed to elucidate the beneficial effect through either receptor dependent or receptor independent neuroprotective mechanisms. Administration of MK886 (1mg/kg, i.p.) prior to fenofibrate (200mg/kg, p.o.) abolished the effect of fenofibrate. The results showed that receptor dependent neuroprotective effects of fenofibrate in 3-NP administered rats provide a new evidence for a role of PPAR-α activation in neuroprotection that is attributed by modulating oxidative stress and inflammation.
authors: Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India. bhatejadeepak@gmail.com
authors: Deepak Kumar
authors: DK
authors: Bhateja
authors: Dinesh K
authors: DK
authors: Dhull
authors: Aneet
authors: A
authors: Gill
authors: Akramdeep
authors: A
authors: Sidhu
authors: Saurabh
authors: S
authors: Sharma
authors: B V Krishna
authors: BV
authors: Reddy
authors: Satyanarayana S V
authors: SS
authors: Padi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005121:Extremities / Q000502:physiology; D011345:Fenofibrate / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism*; D011422:Propionates / Q000633:toxicity*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009573:Nitrites; D009574:Nitro Compounds; D047493:PPAR alpha; D011422:Propionates; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D005978:Glutathione; C015392:3-nitropropionic acid; D011345:Fenofibrate