Cited by 54Parkinson's Disease Mechanisms and TreatmentsNicotinic Acetylcholine Receptors StudyNuclear Receptors and Signaling

Nicotine partially protects against paraquat‐induced nigrostriatal damage in mice; link to α6β2* nAChRs

Khwaja, Mirium, McCormack, Alison, McIntosh, J. Michael, Di Monte, Donato A., Quik, Maryka·2007·Journal of Neurochemistry

Abstract

Epidemiological studies indicate that smoking is a negative, and exposure to pesticides, a positive risk factor for Parkinson's disease (PD). The purpose of this study was to assess the interplay between these two factors in a rodent model of nigrostriatal damage. To approach this, mice were administered nicotine, the agent in smoke implicated in neuroprotection. They were then treated for 3 weeks with the pesticide, paraquat, while nicotine was continued. Paraquat treatment decreased (25%) nigral dopaminergic neurons, consistent with previous results. Chronic nicotine administration significantly protected against nigral cell damage, with only a 16% decline in mice treated with both nicotine and paraquat. Paraquat treatment also decreased (14%) the striatal dopamine transporter, an effect that was partially prevented by nicotine. These changes in the striatal dopamine transporter paralleled those in a select striatal α6β2* nicotinic receptor (nAChR) subtype. In contrast, striatal α4β2* nAChRs were not decreased with paraquat treatment, suggesting they are on a differential subset of dopaminergic terminals. The results show that nicotine treatment partially protects against paraquat‐induced declines in nigrostriatal dopaminergic neurons to which a select population of α6β2* nAChRs are localized. Moreover, these data support epidemiological findings that environmental influences can elicit opposing effects on nigrostriatal dopaminergic integrity.

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Crossref · 10.1111/j.1471-4159.2006.04177.x

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Authors
Khwaja, M., McCormack, A., McIntosh, J. M., Di Monte, D. A., & Quik, M.
Affiliations
  • Parkinson's Institute and Clinical Center (US)
  • University of Utah (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2006-08-21
Volume
100
Issue
1
Pages
180-190
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2017081050
Cited by
54
References
76
Citations by year
2026: 2 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 3
FWCI
5.09
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH53631, R01MH053631)
  • National Institute on Drug Abuse (R01DA012242, DA12242)
  • National Institute of Neurological Disorders and Stroke (R01NS047162, NS42091, NS47162, R01NS042091)
  • National Institute of Environmental Health Sciences (U54ES012077, ES 10806, ES12077, R01ES010806)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
nicotine, paraquat, Parkinson's disease, nigrostriatal dopaminergic neurons, α4β2 nicotinic acetylcholine receptor, dopamine transporter, neuroprotection, pesticide exposure, smoking, dopaminergic terminals
MeSH terms
Analysis of Variance, Animals, Autoradiography, Brain Injuries, Cell Count, Corpus Striatum, Disease Models, Animal, Dopamine, Drug Interactions, Immunohistochemistry, Male, Mice, Inbred C57BL, Neurons, Nicotine, Paraquat, Protein Binding, Pyridines, Receptors, Nicotinic, Substantia Nigra, Nicotinic Agonists, Nicotinic Antagonists, Bridged Bicyclo Compounds, Heterocyclic, Conotoxins, Mice

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