Abstract
Recently, the detailed etiology and pathogenesis of Parkinson's disease (PD) have not been fully clarified yet. Increasing evidences suggested that the disturbance of peripheral branched-chain amino acids (BCAAs) metabolism can promote the occurrence and progression of neurodegenerative diseases through neuroinflammatory signaling. Although there are several studies on the metabolomics of PD, longitudinal study of metabolic pathways is still lacking. Therefore, the purpose of the present study was to determine the longitudinal alterations in serum amino acid profiles in PD mouse model. Gas chromatography-mass spectrometry (GC–MS) was applied to detect serum amino acid concentrations in C57BL/6 mice after 0, 3 and 4 weeks of oral administration with rotenone. Then the data were analysed by principal component analysis (PCA) and orthogonal projection to latent structures (OPLS) analysis. Finally, the correlations between different kinds of serum amino acids and behaviors in rotenone-treated mice were also explored. Compared with 0-week mice, the levels of l-isoleucine and l-leucine were down-regulated in 3-week and 4-week mice, especially in 4-week mice. Moreover, the comprehensive analysis showed that l-isoleucine and l-leucine were negatively correlated with pole-climbing time and positively correlated with fecal weight and water content of PD mice. These results not only suggested that l-isoleucine and l-leucine may be potential biomarkers, but also pointed out the possibility of treating PD by intervening in the circulating amino acids metabolism.
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Abbreviations
- PD:
-
Parkinson's disease
- BCAAs:
-
Branched-chain amino acids
- GC–MS:
-
Gas chromatography–mass spectrometry
- OPLS-DA:
-
Orthogonal projections to latent structures-discriminant analysis
- α-syn:
-
α-Synuclein
- SN:
-
Substantia nigra
- CNS:
-
Central nervous system
- PNS:
-
Peripheral nervous system
- ANOVA:
-
One-way analysis of variance
- SD:
-
Standard deviation
- PLS-DA:
-
Partial least squares discriminant analysis
- CV-ANOVA:
-
Cross-validation ANOVA
- FDR:
-
False discovery rate
- VIP:
-
Variable importance in projection
- ROC:
-
Receiver operating characteristic
- AUC:
-
Area under the ROC curve
- FC:
-
Fold change
- ENS:
-
Enteric nervous system
- mTORC1:
-
Mechanistic target of rapamycin complex 1
- SCFAs:
-
Short chain fatty acids
- SRM:
-
Selective reaction monitor
- RSD:
-
Relative standard deviation
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This work was supported by the National Natural Science Foundation of China [grant numbers 62072143, 81271208].
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Conceptualization: ZY; methodology: ZY, FY, SW, KW and LY; formal analysis: ZY and WD; investigation: ZY; data curation: ZY, YS and RL; writing—original draft preparation: ZY; writing—review and editing: KW and LY; visualization: ZY and WD; supervision: KW and LY; project administration: ZY; funding acquisition: LY. All authors have read and agreed to the published version of the manuscript.
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This animal study was approved by the Animal Use and Care Committee of the First Affiliated Hospital of Harbin Medical University.
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Yan, Z., Yang, F., Wen, S. et al. Longitudinal metabolomics profiling of serum amino acids in rotenone-induced Parkinson's mouse model. Amino Acids 54, 111–121 (2022). https://doi.org/10.1007/s00726-021-03117-1
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DOI: https://doi.org/10.1007/s00726-021-03117-1