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Metabolic Changes Detected by Ex Vivo High Resolution 1H NMR Spectroscopy in the Striatum of 6-OHDA-Induced Parkinson’s Rat

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance (1H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.

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Abbreviations

PD:

Parkinson’s disease

6-OHDA:

6-Hydroxydopamine

GABA:

γ-Aminobutyric acid

Glu:

Glutamate

Gln:

Glutamine

Lac:

Lactate

NAA:

N-acetyl aspartate

Ala:

Alanine

Suc:

Succinate

Asp:

Aspartate

Cr:

Creatine

Tau:

Taurine

m-Ins:

Myo-inositol

Cho:

Choline

Gly:

Glycine

CNS:

Central nervous system

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. 21175099 and 81171306), the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents, and the Zhejiang Provincial Project of Key Scientific Group (2010R50042).

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Authors and Affiliations

  1. School of Pharmacy, Wenzhou Medical College, Wenzhou, 325035, People’s Republic of China

    Hong-Chang Gao, Huan Zhu, Cai-Yong Song, Li Lin, Fa-Qing Ye & Xiao-Kun Li

  2. Radiology Department of the Second Affliated Hospital, Wenzhou Medical College, Wenzhou, 325035, People’s Republic of China

    Zhi-Han Yan & Guang-Hui Bai

  3. Wuhan Medical and Health Center for Women and Children, Huazhong University of Science and Technology, Wuhan, 430015, People’s Republic of China

    Yun Xiang

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  1. Hong-Chang Gao
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Correspondence to Hong-Chang Gao.

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H. Zhu is a co-first author in the present study.

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Gao, HC., Zhu, H., Song, CY. et al. Metabolic Changes Detected by Ex Vivo High Resolution 1H NMR Spectroscopy in the Striatum of 6-OHDA-Induced Parkinson’s Rat. Mol Neurobiol 47, 123–130 (2013). https://doi.org/10.1007/s12035-012-8336-z

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  • DOI: https://doi.org/10.1007/s12035-012-8336-z

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