Integrated transcriptomic and metabolomic analysis of cortical neurons reveals dysregulated lipid metabolism, enhanced glycolysis and activated HIF-1 signaling pathways in acute hypoxia. Issue 4 (April 2023)

• Record Type: Journal Article
• Authors: Zhang, Wenyi; Han, Bo; Zhang, Huijun; Fu, Rao; Lu, Yinzhong; Zhang, Guangming
• Is Part Of: Heliyon. Volume 9:Issue 4(2023)
• Publication Date: 2023-04
• Subjects: Hypoxia -- Neuron -- RNA sequencing -- Metabolomics -- Multi-omics analysis; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2023.e14949
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: The brain is the main oxygen-consuming organ and is vulnerable to ischemic shock or insufficient blood perfusion. Brain hypoxia has a persistent and detrimental effect on resident neurons. Previous studies have identified alterations in genes and metabolites in ischemic brain shock by single omics, but the adaptive systems that neurons use to cope with hypoxia remain uncovered. In the present study, we constructed an acute hypoxia model and performed a multi-omics analysis from RNA-sequencing and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics on exploring potentially differentially expressed genes (DEGs) and metabolites (DEMs) in primary cortical neurons under severe acute hypoxic conditions. The TUNEL assay showed acute hypoxia-induced apoptosis in cortical neurons. Omics analysis identified 564 DEGs and 46 DEMs categorized in the Kyoto encyclopedia of genes and genomes (KEGG) database. Integrative pathway analysis highlighted that dysregulated lipid metabolism, enhanced glycolysis, and activated HIF-1 signaling pathways could regulate neuron physiology and pathophysiology under hypoxia. These findings may help us understand the transcriptional and metabolic mechanisms by which cortical neurons respond to hypoxia and identify potential targets for neuron protection. Highlights: Acute hypoxia induces apoptosis in primary cortical neurons. Acute hypoxia alters the metabolomics and transcriptomics profiles of cortical neurons. Multi-omics analysis shows dysregulated lipid metabolism, enhanced glycolysis and activated HIF-1 signaling.