Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings

The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles o...

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Main Authors: Zhibin Xu, Ye Tian, A.-Xiang Li, Jiahang Tang, Xiao-Yuan Jing, Chunshan Deng, Zhizhun Mo, Jiaxuan Wang, Juan Lai, Xuemei Liu, Xuantong Guo, Tao Li, Shupeng Li, Liping Wang, Zhonghua Lu, Zuxin Chen, Xin-an Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2022.800406/full
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author Zhibin Xu
Zhibin Xu
Ye Tian
Ye Tian
A.-Xiang Li
A.-Xiang Li
Jiahang Tang
Xiao-Yuan Jing
Chunshan Deng
Zhizhun Mo
Jiaxuan Wang
Juan Lai
Xuemei Liu
Xuantong Guo
Tao Li
Shupeng Li
Shupeng Li
Shupeng Li
Liping Wang
Liping Wang
Liping Wang
Zhonghua Lu
Zhonghua Lu
Zhonghua Lu
Zuxin Chen
Zuxin Chen
Zuxin Chen
Zuxin Chen
Xin-an Liu
Xin-an Liu
Xin-an Liu
author_facet Zhibin Xu
Zhibin Xu
Ye Tian
Ye Tian
A.-Xiang Li
A.-Xiang Li
Jiahang Tang
Xiao-Yuan Jing
Chunshan Deng
Zhizhun Mo
Jiaxuan Wang
Juan Lai
Xuemei Liu
Xuantong Guo
Tao Li
Shupeng Li
Shupeng Li
Shupeng Li
Liping Wang
Liping Wang
Liping Wang
Zhonghua Lu
Zhonghua Lu
Zhonghua Lu
Zuxin Chen
Zuxin Chen
Zuxin Chen
Zuxin Chen
Xin-an Liu
Xin-an Liu
Xin-an Liu
author_sort Zhibin Xu
collection DOAJ
description The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.
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spelling doaj.art-1804e1db477d4fb8b83efee1a2e27f9c2022-12-22T00:28:39ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-03-011510.3389/fnmol.2022.800406800406Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic SignalingsZhibin Xu0Zhibin Xu1Ye Tian2Ye Tian3A.-Xiang Li4A.-Xiang Li5Jiahang Tang6Xiao-Yuan Jing7Chunshan Deng8Zhizhun Mo9Jiaxuan Wang10Juan Lai11Xuemei Liu12Xuantong Guo13Tao Li14Shupeng Li15Shupeng Li16Shupeng Li17Liping Wang18Liping Wang19Liping Wang20Zhonghua Lu21Zhonghua Lu22Zhonghua Lu23Zuxin Chen24Zuxin Chen25Zuxin Chen26Zuxin Chen27Xin-an Liu28Xin-an Liu29Xin-an Liu30Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Forensic Medicine, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Forensic Medicine, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, ChinaDepartment of Psychiatry, University of Toronto, Toronto, ON, CanadaKey Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaShenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaThe use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.https://www.frontiersin.org/articles/10.3389/fnmol.2022.800406/fulle-cigarettenicotinementholsocial activityelectronic nicotine delivery systems (ENDS)
spellingShingle Zhibin Xu
Zhibin Xu
Ye Tian
Ye Tian
A.-Xiang Li
A.-Xiang Li
Jiahang Tang
Xiao-Yuan Jing
Chunshan Deng
Zhizhun Mo
Jiaxuan Wang
Juan Lai
Xuemei Liu
Xuantong Guo
Tao Li
Shupeng Li
Shupeng Li
Shupeng Li
Liping Wang
Liping Wang
Liping Wang
Zhonghua Lu
Zhonghua Lu
Zhonghua Lu
Zuxin Chen
Zuxin Chen
Zuxin Chen
Zuxin Chen
Xin-an Liu
Xin-an Liu
Xin-an Liu
Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
Frontiers in Molecular Neuroscience
e-cigarette
nicotine
menthol
social activity
electronic nicotine delivery systems (ENDS)
title Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
title_full Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
title_fullStr Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
title_full_unstemmed Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
title_short Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings
title_sort menthol flavor in e cigarette vapor modulates social behavior correlated with central and peripheral changes of immunometabolic signalings
topic e-cigarette
nicotine
menthol
social activity
electronic nicotine delivery systems (ENDS)
url https://www.frontiersin.org/articles/10.3389/fnmol.2022.800406/full
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