首页|Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics

Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics

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Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)neurons,and accumulating evidence suggests that glia play prominent roles in nicotine addiction.However,VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration.Here,a male mouse model of nicotine self-administration is established and the timing of three critical phases(pre-addiction,addicting,and post-addiction phase)is characterized.Single-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell subtypes.Adaptive changes occurred during the addicting and post-addiction phases,with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell subtype.Furthermore,significant transcriptional changes in energy metabolism-related genes are observed,accompanied by notable structural alterations in neuronal mitochondria during the pro-gression of nicotine self-administration.The results provide insights into mechanisms underlying the pro-gression of nicotine addiction,serving as an important resource for identifying potential molecular targets for nicotine cessation.

Single-nucleus transcriptomicsVentral tegmental areaNicotine addictionCell-type-specific alterationMitochondrial dysfunction

Lei Fan、Boxin Liu、Ru Yao、Xia Gao、Hongjuan Wang、Sanjie Jiang、Xiaomin Zheng、Huan Chen、Hongwei Hou、Yong Liu、Qingyuan Hu

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Anhui Institute of Optics and Fine Mechanics,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei,Anhui 230000,China

University of Science and Technology of China,Hefei,Anhui 230000,China

Beijing Life Science Academy,Beijing 100000,China

Key Laboratory of Tobacco Biological Effects and Biosynthesis,Beijing 100000,China

China National Tobacco Quality Supervision & Test Center,Zhengzhou,Henan 450000,China

Key Laboratory of Tobacco Biological Effects,Zhengzhou,Henan 450000,China

BGI Genomics,BGI-Shenzhen,Guangdong 518018,China

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2024

10.1016/j.jgg.2024.08.009

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(11)