Multi-omics analysis reveals GABAergic dysfunction after traumatic brainstem injury in rats

Qin Su; Qianling Chen; Zhigang Li; Jian Zhao; Lingyue Li; Luyao Xu; Bin Yang; Chao Liu

doi:10.3389/fnins.2022.1003300

Multi-omics analysis reveals GABAergic dysfunction after traumatic brainstem injury in rats

Front Neurosci. 2022 Nov 23:16:1003300. doi: 10.3389/fnins.2022.1003300. eCollection 2022.

Authors

Qin Su^{1

2}, Qianling Chen³, Zhigang Li¹, Jian Zhao¹, Lingyue Li³, Luyao Xu³, Bin Yang³, Chao Liu¹

Affiliations

¹ Guangzhou Forensic Science Institute, Guangzhou, China.
² Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
³ School of Forensic Medicine, Southern Medical University, Guangzhou, China.

Abstract

Background: Traumatic brainstem injury (TBSI) is one of the forms of brain injury and has a very high mortality rate. Understanding the molecular mechanism of injury can provide additional information for clinical treatment.

Materials and methods: In this study, we detected transcriptome, proteomics, and metabolome expression changes in the brainstem of TBSI rats, and comprehensively analyzed the underlying mechanisms of TBSI.

Results: After TBSI, there was significant diffuse axonal injury (DAI) in the brainstem of rats. A total of 579 genes, 70 proteins, and 183 metabolites showed significant changes in brainstem tissue. Through molecular function and pathway analysis, the differentially expressed genes, proteins, and metabolites of TBSI were mainly attributed to neural signal regulation, inflammation, neuroprotection, and immune system. In addition, a comprehensive analysis of transcripts, proteins, and metabolites showed that the genes, proteins, and metabolic pathways regulated in the brainstem after TBSI were involved in neuroactive ligand-receptor interaction. A variety of GCPR-regulated pathways were affected, especially GAGA's corresponding receptors GABA_A, GABA_B, GABA_C, and transporter GAT that were inhibited to varying degrees.

Conclusion: This study provides insights into the development of a rapid diagnostic kit and making treatment strategies for TBSI.

Keywords: GABA; diffuse axonal injury; metabolome; proteome; transcriptome; traumatic brainstem injury.