4.4 Article

Nicotine improved the olfactory impairment in MPTP-induced mouse model of Parkinson's disease

Journal

NEUROTOXICOLOGY
Volume 73, Issue -, Pages 175-182

Publisher

ELSEVIER
DOI: 10.1016/j.neuro.2019.02.008

Keywords

Parkinson's disease; Olfactory dysfunction; Nicotine; cHolinergic system

Funding

  1. National Natural Science Foundation of China [91649114]
  2. Jiangsu Provincial Key RD Program [BE2018658]
  3. Jiangsu Provincial Medical Key Discipline Project [ZDXK132016022]
  4. Suzhou Clinical Research Center of Neurological Disease [Szzx201503]
  5. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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Olfactory impairment is an 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. We observed that nicotine improved locomotor activity and protection against dopaminergic neuron loss in the midbrain in 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 olfactory bulb (OB) in MPTP-treated mice, which was also attenuated by nicotine administration. In addition, nicotine ameliorated the loss of cholinergic neurons and dopaminergic innervation in the horizontal limb of the diagonal band (HDB), which is the primary origin of cholinergic input to the OB. Our results suggested that nicotine could improve the olfactory impairment by protecting cholinergic systems in the OB of MPTP-treated mice. And nicotine protection of cholinergic systems in the OB is relevant to attenuating dopaminergic neuron loss in the midbrain and HDB.

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