Nicotine Improved The Olfactory Function In MPTP-Induced Mouse Model Of Parkinson's Disease

Background:Olfactory impairment is a frequent and early feature of patients with Parkinson's disease(PD).Retrospective epidemiological studies reported lower scores on the University of Pennsylvania Smell Identification Test(UPSIT)in non-smokers than smokers with PD,and showed an inverse correlation between susceptibility to PD and a person's history of smoking.But the mechanisms by which cigarettes affect olfaction in PD are not fully understood.So we investigated the effect of nicotine on the olfactory function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP)-treated mice.Methods:The C57BL/6 mice received intraperitoneal(i.p.)injection with nicotine(1.0 mg/kg)daily for 3 weeks,and/or four injections of MPTP(14 mg/kg,i.p.)at 2-hour intervals to induce PD on the 8th day.In parallel,the control group was given with normal saline(0.9%NaCl).After 21 days of nicotine treatment,motor function was evaluated by rotarod test and open field test.Olfactory function was assessed by buried pellet test,block test and olfactory memory test.The dopaminergic neuron loss in the midbrain was evaluated by tyrosine hydroxylase(TH)which were detected by western blot and Immunohistochemistry.Western blot was also applied to observe the changes of cholinergic system in the olfactory bulb(OB)and the horizontal limb of the diagonal band(HDB).Results:We observed that nicotine improved the locomotor activity and protected against dopaminergic neuron loss in the midbrain of MPTP-treated mice.Compared to controls,MPTP-treated mice showed a deficit of odor discrimination and odor detection,which were alleviated by nicotine treatment.But no significant changes were found in olfactory memory in MPTP-treated mice.Moreover,we detected a marked decrease of choline acetyltransferase(ChAT)expression in the OB of MPTP-treated mice,which was also attenuated by nicotine administration.In addition,nicotine ameliorated the loss of cholinergic neurons and dopaminergic innervation in the HDB,which is the primary origin of cholinergic input to the OB.Conclusion:Our results indicate that nicotine could improve the olfactory impairment by protecting cholinergic systems in the OB of MPTP-treated mice.And that nicotine increase cholinergic systems in the OB is related to attenuated dopaminergic neuron loss in the midbrain.