Neuropsychiatric Disease and Treatment (Jun 2021)
High Mobility Group Box 1/Toll-like Receptor 4 Signaling Increases GABRB3 Expression in Alcohol Exposure
Abstract
Guangtao Sun,1,* Xunzhong Qi,1,* Wei Wang,1,* Xintong Li,1,* Chunhua Luo,2,* Sunjie Bai,3 Shaohua Xu,2 Xiaogang Zhong,4 Chenglong Huang,5 Xiaofeng Zhu,6 Zuoyi Huang1 1Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, People’s Republic of China; 2Department of Laboratory Medicine, Yichang Central People’s Hospital, The First College of Clinical Medical Science, Three Gorges University, Hubei, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Key Laboratory of Psychoseomadsy, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Laboratory Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Mudanjiang Medical College, Mudanjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuoyi Huang Email [email protected]: Prefrontal cortex (PFC) and striatal neurotransmitter homeostasis is affected by alcohol dependence. In this study, the microarray dataset from the Gene Expression Omnibus (GEO) database were downloaded. The prefrontal and striatum data were cross-analyzed to reveal the co-effects of alcohol dependence on the two brain regions of mice.Methods: The GSE123114 microarray profile was downloaded from the GEO database, and differentially expressed genes (DEGs) between the two groups were acquired by GEO2R. KEGG analyses were performed to identify the pivotal pathways of these DEGs. Key differential gene expressions and their mechanism associated with alcohol exposure were investigated by an intraperitoneal alcohol model.Results: A total of 13 overlapping DEGs from the PFC and striatal datasets of the GSE123114 microarray profile were identified, and they were significantly enriched in the morphine addiction pathway. The transcript levels and protein expression of Gabrb3 were consistent with the microarray data both in the PFC and striatum. The transcript levels of HMGB1, TLR4, TNFα and IL-1β were upregulated in the PFC and striatum of mice in the alcohol group. The HMGB1 inhibitor decreased Gabrb3 transcript and protein levels as well as TNFα and IL-1β transcript levels both in the PFC and striatum in the intraperitoneal alcohol model mice.Discussion: Through the reanalysis of GSE123114 microarray profile, we found that Gabrb3 is a key gene associated with alcohol exposure. In further experiments, our findings suggest that alcohol exposure modulates Gabrb3 expression through the HMGB1/TLR4 pathway. Moreover, inflammation-associated factors, such as IL-1β and TNFα, may be related to the HMGB1/TLR4-mediated regulation of GABRB3 expression in alcohol exposure.Keywords: alcohol exposure, prefrontal cortex, striatum, Gabrb3, HMGB1/TLR4 pathway
