N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington's disease.
Mitochondrial dysfunction is a major event involved in the pathogenesis of Huntington's disease (HD). The present study evaluates the role of N-acetyl-L-cysteine (NAC) in preventing mitochondrial dysfunctions in a 3-nitropropionic acid (3-NP)-induced model of HD. Administration of 3-NP to rats (Wistar strain) resulted in significant inhibition of mitochondrial complexes II, IV and V in the striatum. However, no significant effect on complex I was observed. Increased generation of reactive oxygen species and lipid peroxidation was observed in mitochondria of 3-NP-treated animals. Endogenous antioxidants (thiols and manganese-superoxide dismutase) were lowered in mitochondria of 3-NP-treated animals. 3-NP-treated animals showed increased cytosolic cytochrome c levels and mitochondrial swelling. Increased expressions of caspase-3 and p53 were also observed in 3-NP-treated animals. Histopathological examination of the striata of 3-NP-treated animals revealed increased neural space, neurodegeneration and gliosis. This was accompanied by cognitive and motor deficits. NAC treatment, on the other hand, was found to be effective in reversing 3-NP-induced mitochondrial dysfunctions and neurobehavioral deficits. Our findings suggest a beneficial effect of NAC in HD.
Department of Biochemistry, Panjab University, Chandigarh, India. sandhir@pu.ac.in
Rajat
R
Sandhir
Aditi
A
Sood
Arpit
A
Mehrotra
Sukhdev S
SS
Kamboj
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009048:Motor Skills / Q000187:drug effects*; D009574:Nitro Compounds / Q000506:poisoning*; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000506:poisoning*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016166:Free Radical Scavengers; D009574:Nitro Compounds; D011422:Propionates; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase; D053148:Caspase 3; C015392:3-nitropropionic acid; D000111:Acetylcysteine