title: Mitochondrial cofactors in experimental Huntington's disease: behavioral, biochemical and histological evaluation.
abstract: The present study was carried out to evaluate the beneficial effect of mitochondrial cofactors; alpha-lipoic acid (ALA) and acetyl-l-carnitine (ALCAR) in 3-nitropropionic acid (3-NP) induced experimental model of Huntington's disease (HD). HD was developed by administering sub-chronic doses of 3-NP, intraperitoneally, twice daily for 17 days. The animals were assessed for their behavioral performance in terms of motor (spontaneous locomotor activity, narrow beam walk test, footprint analysis and rotarod test) and cognitive (elevated plus maze and T-maze tests) functions. 3-NP treated animals showed impairment in motor coordination such as decreased stride length, increased distance between inner toes, and increased gait angle. Increased transfer latency on elevated plus maze and T-maze tasks revealed cognition deficits in 3-NP treated animals. Increased lipid peroxidation and concomitant decrease in thiol levels were also observed. 3-NP administration also induced histopathological changes in terms of enhanced striatal lesion volume, presence of pyknotic nuclei and astrogliosis. However, combined supplementation with ALA+ALCAR to 3-NP administered animals for 21 days was able to efficiently improve behavioral deficits, attenuate oxidative stress and histological changes, suggesting a putative role of these two supplements if given together in ameliorating 3-NP induced impairments and thus could be engaged in managing HD.
authors.affiliation: Department of Biochemistry, Basic Medical Science Building, Panjab University, Sector-14, Chandigarh 160014, India.
authors.forename: Arpit
authors.initials: A
authors.lastname: Mehrotra
authors.affiliation: Department of Biochemistry, Basic Medical Science Building, Panjab University, Sector-14, Chandigarh 160014, India. Electronic address: sandhir@pu.ac.in.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006816:Huntington Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009574:Nitro Compounds / Q000627:therapeutic use; D011422:Propionates / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D008063:Thioctic Acid / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D009574:Nitro Compounds; D011422:Propionates; D000108:Acetylcarnitine; D008063:Thioctic Acid; D005978:Glutathione; C015392:3-nitropropionic acid
keywords: 2,3,5-triphenyltetrazolium chloride; 3,3′-di-aminobenzidine; 3-NP; 3-nitropropionic acid; ALA; ALCAR; Acetyl-l-carnitine; Alpha-lipoic acid; Behavior; DAB; GFAP; GSH; HD; Huntington's disease; MDA; Mitochondria; TTC; acetyl-l-carnitine; alpha-lipoic acid; glial fibrillary acidic protein; glutathione; malondialdehyde