Dataset Information

Stable isotope-resolved metabolomics reveals the abnormal brain glucose catabolism in depression based on chronic unpredictable mild stress rats

ABSTRACT: The severe harm of depression to human life has attracted great attention to neurologists, but its pathogenesis is extremely complicated and has not yet been fully elaborated. Here, we provided a new strategy for revealing the specific pathways of abnormal brain glucose catabolism in depression, which from the supply of energy substrates and the evaluation of mitochondrial structure and function. By using stable isotope-resolved metabolomics technique, we discovered the tricarboxylic acid cycle (TCA cycle) is blocked and the gluconeogenesis is abnormally activated in chronic unpredictable mild stress (CUMS) rats. In addition, our results showed an interesting phenomenon that the brain attempted to activate all possible metabolic enzymes in energy-producing pathways, but CUMS rats still exhibited a low TCA cycle activity due to impaired mitochondria. Depression caused mitochondrial structure and function impaired, and then led to abnormal brain glucose catabolism. The combination of the stable isotope-resolved metabolomics and mitochondrial structure and function analysis can accurately clarify the mechanism of depression. The mitochondrial pyruvate carrier and acetyl-CoA maybe the key targets for depression treatment. The strategy provides a unique insight for exploring the mechanism of depression, the discovery of new targets, and the development of ideal novel antidepressants.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Ting Linghu

LAB HEAD: Xuemei Qin

PROVIDER: PXD025548 | Pride | 2021-06-10

REPOSITORIES: Pride

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Stable Isotope-Resolved Metabolomics Reveals the Abnormal Brain Glucose Catabolism in Depression Based on Chronic Unpredictable Mild Stress Rats.

Ling-Hu Ting T Liu Shao-Bo SB Gao Yao Y Han Yu-Mei YM Tian Jun-Sheng JS Qin Xue-Mei XM

Journal of proteome research 20210602 7

The severe harm of depression to human life has attracted great attention to neurologists, but its pathogenesis is extremely complicated and has not yet been fully elaborated. Here, we provided a new strategy for revealing the specific pathways of abnormal brain glucose catabolism in depression, based on the supply of energy substrates and the evaluation of the mitochondrial structure and function. By using stable isotope-resolved metabolomics, we discovered that the tricarboxylic acid cycle (TC ...[more]

PMID: 34077228

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