Exp Neurobiol.  2008 Dec;17(2):95-100. 10.5607/en.2008.17.2.95.

Nicotine Prevents MPTP-induced Dopaminergic Neurodegeneration

• Kim JM
• O JJ
• Jeon BS

• KMID: 2165288
• DOI: http://doi.org/10.5607/en.2008.17.2.95

Abstract

Epidemiological studies of Parkinson disease (PD) have found an inverse correlation between cigarette smoking and the risk of developing PD, which suggests that nicotine has a protective effect. Results from animal models of PD are conflicting, raising questions about a protective potential of nicotine. In this study, mice were pretreated with low-dose nicotine before MPTP administration, and examined to determine a neuroprotective potential of nicotine. The schedule of nicotine administration was selected to simulate the future human trials using this putative neuroprotective agent. Male C57Bl/6 mice were pretreated with nicotine for 5 days (0.2 mg/kg/d, i.p.). After the 5-day-pretreatment with nicotine only, nicotine and MPTP (30 mg/kg/d, i.p.) were co-administered for 1 to 5 consecutive days. The total dose of nicotine, 0.2 mg/kg/d for 6 to 10 days, is the lowest one ever studied. Tyrosine hydroxylase (TH) immunohistochemical staining of the nigral sections was performed. Over the experimental period, there was a significant reduction in the TH-positive cells. In the nicotine-MPTP group, the degree of TH neuron depletion was reduced at days 4 and 5 of co-administration. These findings suggest that the nicotinic neurotransmission on the dopaminergic neurons are promising targets for neuroprotective therapy of PD.

Keyword

MPTP; nicotine; Parkinson disease; smoking

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Appointments and Schedules
Dopaminergic Neurons
Humans
Male
Mice
Models, Animal
Neurons
Nicotine
Parkinson Disease
Smoking
Synaptic Transmission
Tyrosine 3-Monooxygenase
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Nicotine
Tyrosine 3-Monooxygenase