Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats.
Nicotinic acetylcholine receptors (nAChRs) are regarded as potential therapeutic targets to control various neurodegenerative diseases. Owing to the relevance of cholinergic neurotransmission in the pathogenesis of Huntington's disease (HD) this investigation was aimed to study the effect of nicotine, a nAChR agonist, on 3-nitropropionic acid (3-NP)-induced neurodegeneration in female Wistar rats. Systemic administration of 3-NP in rats serves as an important model of HD. The animals received subcutaneous injections of nicotine (0, 0.25, 0.50 and 1.00 mg/kg) daily for 7 days. 3-NP (25 mg/kg, i.p.) was administered daily 30 min after nicotine for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance (motor activity, inclined plane test, grip strength test, paw test and beam balance). Immediately after behavioral studies, the animals were transcardially perfused with neutral buffered formalin (10%) and brains were fixed for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase (TH) immunostaining. Treatment of rats with nicotine significantly and dose-dependently attenuated 3-NP-induced behavioral deficits. Administration of 3-NP alone caused significant depletion of striatal dopamine (DA) and glutathione (GSH), which was significantly and dose-dependently attenuated by nicotine. Preservation of striatal dopaminergic neurons by nicotine was also confirmed by immunohistochemical studies. These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.
Tariq
Mohammad
M
Neuroscience Research Group, Armed Forces Hospital, P.O. Box 7897 (W-912), Riyadh 11159, Saudi Arabia. rkh_research.yahoo.com
Khan
Haseeb Ahmad
HA
Elfaki
Ibrahim
I
Al Deeb
Saleh
S
Al Moutaery
Khalaf
K
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D009574:Nitro Compounds; D011422:Propionates; D011978:Receptors, Nicotinic; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D005978:Glutathione; C015392:3-nitropropionic acid; D004298:Dopamine