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

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 protei...