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Brain Region-Specific nAChR and Associated Protein Abundance Alterations Following Chronic Nicotine and/or Menthol Exposure

Mulcahy, Matthew J. and Huard, Stephanie M. and Paulo, Joao A. and Wang, Jonathan H. and McKinney, Sheri and Henderson, Brandon J. and Lester, Henry A. (2020) Brain Region-Specific nAChR and Associated Protein Abundance Alterations Following Chronic Nicotine and/or Menthol Exposure. Journal of Proteome Research, 19 (1). pp. 36-48. ISSN 1535-3893. PMCID PMC7289315. doi:10.1021/acs.jproteome.9b00286.

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The identification of biomarkers that are altered following nicotine/tobacco exposure can facilitate the investigation of tobacco-related diseases. Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian central and peripheral nervous systems and the neuromuscular junction. Neuronal nAChR subunits (11) have been identified in mammals (α2-7, α9-10, β2-4). We examined changes in β2 nAChR subunit protein levels after chronic nicotine, (±)-menthol, or nicotine co-administered with (±)-menthol in nine murine brain regions. Our investigation of β2 nAChR subunit level changes identified the hypothalamus as a novel region of interest for menthol exposure that demonstrated increased β2 nAChR levels after (±)-menthol plus nicotine exposure compared to nicotine exposure alone. Using mass spectrometry, we further characterized changes in membrane protein abundance profiles in the hypothalamus to identify potential biomarkers of (±)-menthol plus nicotine exposure and proteins that may contribute to the elevated β2 nAChR subunit levels. In the hypothalamus, 272 membrane proteins were identified with altered abundances after chronic nicotine plus menthol exposure with respect to chronic nicotine exposure without menthol. A comprehensive investigation of changes in nAChR and non-nAChR protein expression resulting from (±)-menthol plus nicotine in the brain may establish biomarkers to better understand the effects of these drugs on addiction and addiction-related diseases.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Mulcahy, Matthew J.0000-0001-5588-8762
Huard, Stephanie M.0000-0002-2333-1852
Paulo, Joao A.0000-0002-4291-413X
Henderson, Brandon J.0000-0003-0381-028X
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2019 American Chemical Society. Received: April 30, 2019; Published: October 28, 2019. We also thank Dr. Steven P. Gygi and the Taplin Mass Spectrometry Facility at Harvard Medical School for use of their mass spectrometers and access to their Sequest-based data analysis suite. Author Contributions: The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript. M.J.M., S.M.H., J.A.P., B.J.H., and H.A.L. conceived and designed experiments. M.J.M., S.M.H., and J.A.P. performed the experiments. J.A.P., J.H.W., and S.M. contributed reagents/materials/analysis tools. M.J.M. wrote the manuscript. M.J.M., S.M.H., J.A.P., B.J.H., and H.A.L. edited the manuscript. This research was supported by NIH R01DA036061 (H.A.L.) and R01GM132129 (J.A.P.). The authors declare no competing financial interest. The mass spectrometry proteomics data have been deposited to the PRIDE Archive ( via the PRIDE partner repository with the data set identifier PXD012244.(69)
Funding AgencyGrant Number
Subject Keywords:β2 nAChR subunit, nicotine, menthol, immunoblotting, mass spectrometry, addiction
Issue or Number:1
PubMed Central ID:PMC7289315
Record Number:CaltechAUTHORS:20191028-111942058
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Official Citation:Brain Region-Specific nAChR and Associated Protein Abundance Alterations Following Chronic Nicotine and/or Menthol Exposure. Matthew J. Mulcahy, Stephanie M. Huard, Joao A. Paulo, Jonathan H. Wang, Sheri McKinney, Brandon J. Henderson, and Henry A. Lester. Journal of Proteome Research 2020 19 (1), 36-48. DOI: 10.1021/acs.jproteome.9b00286
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99486
Deposited By: Tony Diaz
Deposited On:28 Oct 2019 19:43
Last Modified:16 Nov 2021 17:46

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