Transcriptomics and metabolomics reveal hypothalamic metabolic characteristics and key genes after subarachnoid hemorrhage in rats.
Zongchi LiuZhaohui ChaiFan WuLuyuan ZhangYuxiang WengZihan XuYuxiang WengJiangbiao GongJian ShenRen-Ya ZhanYu ZhuPublished in: Metabolic brain disease (2024)
Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.
Keyphrases
- mass spectrometry
- subarachnoid hemorrhage
- signaling pathway
- pi k akt
- genome wide
- liquid chromatography
- transcription factor
- single cell
- gene expression
- brain injury
- cerebral ischemia
- ms ms
- genome wide identification
- end stage renal disease
- dna methylation
- bioinformatics analysis
- oxidative stress
- cell proliferation
- newly diagnosed
- chronic kidney disease
- high glucose
- genome wide analysis
- type diabetes
- high resolution
- high resolution mass spectrometry
- rna seq
- multiple sclerosis
- cardiovascular disease
- blood brain barrier
- coronary artery disease
- drug induced
- peritoneal dialysis
- cardiovascular events
- prognostic factors
- patient reported
- solid phase extraction
- resting state