Potential Genes and Mechanisms Linking Intracerebral Hemorrhage and Depression: A Bioinformatics-Based Study

Abstract

Purpose The purpose of this study was to investigate the potential pathogenic mechanisms of post-intracerebral hemorrhage depression. Methods Profiles of gene expression in brain tissue of patients with intracerebral hemorrhage (ICH) or depression were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes (DEGs) for the two diseases separately. With these DEGs, we conducted an enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) as well as cross-talk analysis, then we identified hub bridge genes using integrated bridge landscape analysis. Results We found 131 DEGs for interaction between ICH and depression. In the enrichment analysis, we found 55 GO terms and KEGG pathways involving interacting genes of ICH and depression, and 10 GO terms and 10 KEGG pathways most significantly related to cross-talk between ICH and depression. In the integrated bridge landscape analysis, we identified 20 hub bridge genes. In further analysis, we found that hub bridge genes HLA-A, HMOX1 , and JUN related to endocytosis, cell adhesion, and phagosomes may exert their effects through the dopamine (DA) system and the serotonergic pathway post-ICH depression. HLA-A may play a role in the occurrence and development of ICH and depression through immune mediation and cell adhesion. HMOX1 and JUN may participate in the mechanism by interacting with HLA-A . Conclusion Through bioinformatics analysis, we identified potential hub bridge genes and pathways related to post-ICH depression. Our study provides references for further research on mechanisms on the pathogenesis of post-ICH depression.

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

“…Depression after ICH significantly affects prognosis, and Jun is the central gene in the post-ICH depression gene regulatory network [ 34 ]. Jun-related products are also involved in inflammation, stress response [ 35 ] and the development of central nervous system diseases.…”

Novel targets, treatments, and advanced models for intracerebral haemorrhage

“…Some studies suggest rodents with ICH exhibit deficits in the elevated plus maze, sucrose preference, tail suspension, open field, and forced swim tests, 73 , 74 but others have failed 75 resulting in uncertainty whether animal models accurately reflect cognition and depression. 66 Recent studies have investigated genetic links between ICH and depression 76 and the results support the monoaminergic hypothesis, as well as the idea that pro-inflammatory cytokines may stimulate the hypothalamic pituitary adrenal axis. 77 …”

Bidirectional causal association between ischemic stroke and five mental disorders

“…Although the exact mechanism of ischemic stroke leading to Depression is not clear, a study has found 72 interactive genes and 24 functional pathways that both ischemic stroke and depression are involved in through the analysis of the two. These functions and pathways involve chemokines, cytokines, lipid metabolism, amino acid transport, protein alkylation, protein methylation, etc., and these pathways and genes may be involved in the pathogenesis of post‐stroke depression 24 . Another study found that the mechanism of post‐stroke depression is related to the imbalance of GABA expression, the decrease of GABA can lead to the decrease of noradrenaline, 25 and amino acid neurotransmission dysfunction is one of the pathophysiological mechanisms of depression.…”

“…These functions and pathways involve chemokines, cytokines, lipid metabolism, amino acid transport, protein alkylation, protein methylation, etc., and these pathways and genes may be involved in the pathogenesis of post-stroke depression. 24 Another study found that the mechanism of post-stroke depression is related to the imbalance of GABA expression, the decrease of GABA can lead to the decrease of noradrenaline, 25 and amino acid neurotransmission dysfunction is one of the pathophysiological mechanisms of depression. Post-stroke depression is often accompanied by changes in frontal lobe glutamate levels, and the ratio of glutamate/creatinine in the frontal lobe and anterior cingulate gyrus is significantly increased, 26 and glutamate receptor ligands have antidepressant effects.…”