Peripheral tissues metabolites and biological functions in Post-stroke Depression

Abstract

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral tissues metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral tissues of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was “phenylalanine metabolism” and the pathway containing the most associated molecules was “aminoacyl-tRNA biosynthesis”, which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral tissues are associated with PSD, especially the disruption of “phenylalanine metabolism” and “aminoacyl-tRNA biosynthesis” pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD.