<b>Background and Objective:</b> Nicotine-relevant smoking causes many serious issues of environmental pollution and complicated harm to human health. The present study aimed to evaluate the experimental effects of exposure to nicotine on the gene expression profiles of rat brain tissues with differentially expressed genes (DEGs). <b>Materials and Methods:</b> The rat gene expression profiles of environmental exposure to nicotine were initially screened and retrieved from the microarray dataset GSE59895 in the GEO database. Next, it was analyzed with an integrated bioinformatics pipeline. The DEGs were analyzed in Limma and functional enrichment analyses of GO terms and KEGG pathways were performed with clusterProfiler. The STRING online tools and Cytoscape StringApp were subsequently employed to construct the protein-protein interaction (PPI) network, whereas key modules and hub genes were finally explored and visualized. <b>Results:</b> There was total of 382 shared DEGs between different case groups in the experiment, whereas 9 common shared DEGs were found among all three groups. The significant enrichments of 28 GO terms and 3 KEGG pathways were comprehensively analyzed with corresponding functionally enriched genes. Then, 3 key modules and 10 hub genes were further identified and explored in the resulted PPI network. In the disease-related signaling pathways, eleven potential neuropathic disease-related genes may complement the treatment of neurodegenerative diseases. <b>Conclusion:</b> The study found that chronic exposure to nicotine would result in the differential expression of the disease-related genes, whereas these DEGs might increase the environmental risks of Huntington's disease, Alzheimer's disease and other multiple neurodegenerative diseases.
Keywords: Nicotine exposure; brain tissue; differentially expressed genes; neurodegenerative disease; rat brain.