E-cigarette aerosols containing nicotine modulate nicotinic acetylcholine receptors and astroglial glutamate transporters in mesocorticolimbic brain regions of chronically exposed mice. (5th January 2021)

• Record Type: Journal Article
• Authors: Alasmari, Fawaz; Crotty Alexander, Laura E.; Hammad, Alaa M.; Horton, Austin; Alhaddad, Hasan; Schiefer, Isaac T.; Shin, John; Moshensky, Alexander; Sari, Youssef
• Is Part Of: Chemico-biological interactions. Volume 333(2021)
• Publication Date: 2021-01-05
• Subjects: E-cigarettes -- Nicotine -- α4/β2 nAChR -- α-7 nAChR -- GLT-1 -- xCT; AC air control -- ARC activity-regulated cytoskeleton-associated protein -- α-7 nAChR alpha-7 nicotinic acetylcholine receptor -- α4/β2 nAChR alpha 4/ beta 2 nAChR -- BDNF brain-derived neurotrophic factor -- e-cigarette electronic cigarette -- Veh e-cigarette vehicle control -- ECN e-cigarette aerosol-containing nicotine -- FC frontal cortex -- GLAST glutamate/aspartate transporter -- GLT-1 Glutamate transporter-1 -- HIP hippocampus -- NAc nucleus accumbens -- PFC prefrontal cortex -- STR striatum -- VTA ventral tegmental area -- xCT cystine/glutamate antiporter; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109308
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Nicotine exposure increases the release of glutamate in part through stimulatory effects on pre-synaptic nicotinic acetylcholine receptors (nAChRs). To assess the impact of chronic electronic (e)-cigarette use on these drug dependence pathways, we exposed C57BL/6 mice to three types of inhalant exposures for 3 months; 1) e-cigarette aerosol generated from liquids containing nicotine (ECN), 2) e-cigarette aerosol generated from liquids containing vehicle chemicals without nicotine (Veh), and 3) air only (AC). We investigated the effects of daily e-cigarette exposure on protein levels of α7 nAChR and α4/β2 nAChR, gene expression and protein levels of astroglial glutamate transporters, including glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT), in the frontal cortex (FC), striatum (STR) and hippocampus (HIP). We found that chronic inhalation of ECN increased α4/β2 nAChR in all brain regions, and increased α7 nAChR expression in the FC and STR. The total GLT-1 relative mRNA and protein expression were decreased in the STR. Moreover, GLT-1 isoforms (GLT-1a and GLT-1b) were downregulated in the STR in ECN group. However, inhalation of e-cigarette aerosol downregulated xCT expression in STR and HIP compared to AC and Veh groups. ECN group had increased brain-derived neurotrophic factor in the STR compared to control groups. Finally, mass spectrometry detected high concentrations of the nicotine metabolite, cotinine, in the FC and STR in ECN group. This work demonstrates that chronic inhalation of nicotine within e-cigarette aerosols significantly alters the expression of nAChRs and astroglial glutamate transporters in specific mesocorticolimbic brain regions. Highlights: E-cigarette-nicotine exposure for 3 months upregulated α4/β2 nAChR in FC, STR and HIP. E-cigarette-nicotine exposure for 3 months upregulated α7 nAChR in FC and STR. E-cigarette-nicotine exposure for 3 months downregulated GLT-1 and GLT-1 isoforms in STR. E-cigarette vapors-nicotine exposure for 3 months downregulated xCT in STR and HIP. E-cigarette-nicotine exposure for 3 months increased BDNF expression in STR.