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Metabolomic changes in animal models of depression: a systematic analysis

Juncai Pu, Yi-Yun Liu, Siwen Gui, Lu Tian, Yue Yu, Xuemian Song, Xiaogang Zhong, Xiao-Peng Chen et al.

Molecular Psychiatry, 2021

86 citations

Abstract

Extensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and…

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