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Region specific proteomic analysis of murine brain after chronic nicotine or menthol

Mulcahy, Matthew J. and Wang, Jonathan H. and Lester, Henry A. (2017) Region specific proteomic analysis of murine brain after chronic nicotine or menthol. FASEB Journal, 31 (S1). Art. No. 991.1. ISSN 0892-6638.

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Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels that are expressed in the mammalian central nervous system, the peripheral nervous system, and the neuromuscular junction. Eleven neuronal nAChR subunits have been identified in mammals (α2-7, α9-10, β2-4). Chronic administration of nicotine has been shown to increase total α4 and β2 subunit expression in specific brain regions. Menthol, a common cigarette flavoring, has also been shown to upregulate α4 and β2 subunit expression in the cortex, hippocampus, and striatum independent of nicotine co-administration. These data highlight the potential use of changes in β2 nAChR subunit expression as a marker for neuronal nicotine exposure when administered alone and when administered with additional bioactive compounds such as menthol. We investigated the effect of nicotine and of menthol in several murine brain regions on changes in total β2 subunit protein expression using western blot analysis. Absence of β2 immunoreactivity was confirmed in both β2 knockout and α4 knockout mice. To assess the effects of nicotine, male C57bl/6 mice were separated into two treatment groups: control (saline) and nicotine (2mg/kg/hr). Vehicle (ethanol) and menthol alone (2mg/kg/hr) were compared separately. All treatments were administered for 10–12 days. Nicotine-induced β2 immunoreactivity was significantly upregulated in isolated brain regions, including the cortex, hippocampus, midbrain, striatum, and thalamus. No change in immunoreactivity was observed in the habenula of mice treated chronically with nicotine. In response to chronic menthol treatment, a significant increase was only observed in the hypothalamus. These data indicate that nicotine and menthol differentially effect expression of nAChR subtypes in various regions of the brain. A comprehensive analysis of changes in β2 nAChR subunit expression in various brain regions will facilitate our understanding of the effects of nicotine exposure in the mammalian CNS. Additionally, the validation of a reliable marker for nicotine and menthol exposure in regions associated with various aspects of addiction and dependence would be invaluable in the pursuit of better cessation therapeutics. Using β2 expression as a marker of nicotine exposure will enable a better understanding of possible effects of nicotine and menthol.

Item Type:Article
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Mulcahy, Matthew J.0000-0001-5588-8762
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2017 by the Federation of American Societies for Experimental Biology. This work is supported by NIH DA036061.
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Issue or Number:S1
Record Number:CaltechAUTHORS:20170921-153023998
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Official Citation:Matthew J Mulcahy, Jonathan H Wang, and Henry A Lester Region specific proteomic analysis of murine brain after chronic nicotine or menthol FASEB J April 2017 31:991.1
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:81709
Deposited By: Tony Diaz
Deposited On:21 Sep 2017 23:27
Last Modified:09 Mar 2020 13:19

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