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NMR-Based Metabolomics Reveal a Recovery from Metabolic Changes in the Striatum of 6-OHDA-Induced Rats Treated with Basic Fibroblast Growth Factor

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Abstract

Basic fibroblast growth factor (bFGF) has a potential role in the treatment of Parkinson’s disease (PD) due to its neurotrophic effect on dopaminergic neurons. To address the metabolic mechanisms of bFGF administration on PD, we have analyzed the metabolic profiles in the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats after the treatment with bFGF using 1H NMR spectroscopy and partial least squares-discriminant analysis (PLS-DA). In the present study, we found that bFGF treatment can effectively recover PD-induced loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. Metabolomic analyses reveal that PLS-DA failed to discriminate between the control and bFGF groups, indicating that the metabolic difference between these two groups was negligible. However, reliable PLS-DA models can be developed between control and PD groups as well as between PD and bFGF groups, which is attributed to changes in a series of metabolites including GABA, glutamate (Glu), glutamine (Gln), lactate, N-acetylaspartate, creatine, taurine, and myo-inositol. ANOVA results show that the levels of all these metabolites were significantly increased in PD rats relative to normal rats, while PD-induced increase can be significantly reduced to normal levels after bFGF administration. In conclusion, our results suggest that a recovery from PD-induced metabolic disorders may be achieved by bFGF treatment, involving Gln/Glu-GABA cycle, energy metabolism, osmoregulation, and inflammation.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

Ala:

Alanine

bFGF:

Basic fibroblast growth factor

Cho:

Choline

CNS:

Central nervous system

Cre:

Creatine

Eth:

Ethanol

GABA:

γ-Aminobutyric acid

Gln:

Glutamine

Glu:

Glutamate

Lac:

Lactate

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Myo:

Myo-inositol

NAA:

N-acetyl aspartate

PD:

Parkinson’s disease

PLS-DA:

Partial least squares-discriminant analysis

Suc:

Succinate

Tau:

Taurine

TH:

Tyrosine hydroxylase

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos.: 21175099, 21575105, 81400863) and Zhejiang Provincial Natural Science Foundation (Nos.: LY13H070005, LY14H090014, LY15H180010).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China

    Hong Zheng, Liangcai Zhao, Huanhuan Xia, Cuicui Xu, Dan Wang, Li Lin, Xiaokun Li & Hongchang Gao

  2. Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Kun Liu & Zhihan Yan

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  1. Hong Zheng
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Correspondence to Zhihan Yan or Hongchang Gao.

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Zheng, H., Zhao, L., Xia, H. et al. NMR-Based Metabolomics Reveal a Recovery from Metabolic Changes in the Striatum of 6-OHDA-Induced Rats Treated with Basic Fibroblast Growth Factor. Mol Neurobiol 53, 6690–6697 (2016). https://doi.org/10.1007/s12035-015-9579-2

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