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Peer-reviewedCC BY 4.0Frontiers in Neuroscience

Nicotine and tobacco smoke reshape neuronal signaling networks from a single-nucleus transcriptomic perspective

6 affiliations
  1. 1China Tobacco Zhejiang Industrial Co., Ltd.
  2. 2China Tobacco Sichuan Industrial Co., Ltd.
  3. 3Department of Pharmacology, Hangzhou City University School of Medicine
  4. 4Shulan International Medical College, Zhejiang Shuren University
  5. 5Department of Pharmacology, Zhejiang University School of Medicine
  6. 6China National Tobacco Quality Supervision and Test Center

Abstract

Nicotine and cigarette smoke exposure significantly impact brain function, yet their distinct cellular and molecular mechanisms remain unclear. To address this, we conducted comprehensive single-nucleus RNA sequencing (snRNA-seq) analysis on whole-brain samples and specifically on the ventral tegmental area (VTA) of adult C57BL/6 mice following nicotine or smoke exposure. Our study identified 18 major transcriptionally distinct cell populations across the whole brain and 27 distinct clusters within the VTA, covering major neuronal and glial cell types. Differential gene expression and KEGG pathway enrichment analyses revealed distinct transcriptional responses: nicotine exposure was associated with enrichment of synaptic and addiction-related transcriptional pathways in neuronal populations, including dopaminergic and glutamatergic pathways, whereas smoke exposure was associated with broader enrichment of metabolic-, immune-, and endocrine-related pathways. CellChat predicted condition-associated communication differences, including higher inferred NRXN communication from excitatory neurons to oligodendrocytes and other excitatory neurons under nicotine exposure. Smoke exposure also increased oligodendrocyte PISD expression, a transcriptomic change potentially associated with mitochondrial phospholipid metabolism. Collectively, these data define cell-type-specific transcriptional and predicted communication signatures of nicotine and smoke exposure that require functional validation.

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BibTeX
@article{jiang2026nicotine,
  title = {{Nicotine and tobacco smoke reshape neuronal signaling networks from a single-nucleus transcriptomic perspective}},
  author = {Jian Jiang and Anfu Hu and Yixiao Jin and Xia Li and Guo-Jun Zhou and Yi Shen and Chengyun Xu and Xing Ji and Ximei Wu and Hong-Juan Wang},
  journal = {Frontiers in Neuroscience},
  year = {2026},
  month = oct,
  doi = {10.3389/fnins.2026.1953804},
  url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1953804/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Nicotine and tobacco smoke reshape neuronal signaling networks from a single-nucleus transcriptomic perspective
AU  - Jian Jiang
AU  - Anfu Hu
AU  - Yixiao Jin
AU  - Xia Li
AU  - Guo-Jun Zhou
AU  - Yi Shen
AU  - Chengyun Xu
AU  - Xing Ji
AU  - Ximei Wu
AU  - Hong-Juan Wang
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Neuroscience
DO  - 10.3389/fnins.2026.1953804
UR  - https://www.frontiersin.org/articles/10.3389/fnins.2026.1953804/full
AB  - Nicotine and cigarette smoke exposure significantly impact brain function, yet their distinct cellular and molecular mechanisms remain unclear. To address this, we conducted comprehensive single-nucleus RNA sequencing (snRNA-seq) analysis on whole-brain samples and specifically on the ventral tegmental area (VTA) of adult C57BL/6 mice following nicotine or smoke exposure. Our study identified 18 major transcriptionally distinct cell populations across the whole brain and 27 distinct clusters within the VTA, covering major neuronal and glial cell types. Differential gene expression and KEGG pathway enrichment analyses revealed distinct transcriptional responses: nicotine exposure was associated with enrichment of synaptic and addiction-related transcriptional pathways in neuronal populations, including dopaminergic and glutamatergic pathways, whereas smoke exposure was associated with broader enrichment of metabolic-, immune-, and endocrine-related pathways. CellChat predicted condition-associated communication differences, including higher inferred NRXN communication from excitatory neurons to oligodendrocytes and other excitatory neurons under nicotine exposure. Smoke exposure also increased oligodendrocyte PISD expression, a transcriptomic change potentially associated with mitochondrial phospholipid metabolism. Collectively, these data define cell-type-specific transcriptional and predicted communication signatures of nicotine and smoke exposure that require functional validation.
SN  - 1662-453X
SN  - 1662-4548
ER  -