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Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson's disease

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Summary

High-performance liquid chromatography with electrochemical detection has been employed to analyze ultrafiltrates of cerebrospinal fluid of Parkinson's Disease (PD) patients and age-matched controls for the dopamine (DA) metabolites homovanillic acid (HVA) and 5-S-cysteinyldopamine (5-S-CyS-DA). The mean level of HVA in the CSF of PD patients, measured 5 days after withdrawal from L-DOPA therapy, was significantly lower than that measured in controls. By contrast, mean levels of 5-S-CyS-DA were not significantly different in the CSF of PD patients taking L-DOPA (PD-LT patients) the same patients 5 days after discontinuing this drug (PD-LW patients) or controls. However, the mean 5-S-CyS-DA/HVA concentration ratio was significantly (p < 0.05) higher in the CSF of PD-LW patients compared to controls. Although the PD patient population employed in this study had been diagnosed with the disease several years previously and had been treated with L-DOPA for prolonged periods of time the results of this study suggest that low CSF levels of HVA and a high 5-S-CyS-DA/HVA ratio together might represent useful markers for early diagnosis of PD. The high 5-S-CyS-DA/HVA ratio observed in the CSF of PD-LW patients also provides support for the hypothesis that the translocation of glutathione or L-cysteine into neuromelanin-pigmented dopaminergic cell bodies in the substantia nigra might represent an early event in the pathogenesis of PD.

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Abbreviations

CSF :

cerebrospinal fluid

CySH :

L-cysteine

DA :

dopamine

DA-o-quinone :

dopamine-o-quinone

L-DOPA :

3,4-dihydroxyphenylalanine

DOPAC :

3,4-dihydroxyphenylacetic acid

EPI :

epinephrine

GSH :

glutathione

GSSG :

oxidized glutathione

5-HIAA :

5-hydroxyindole-3-acetic acid

HVA :

homovanillic acid

HO·:

hydroxyl radical

HPLC-EC :

high performance liquid chromatography with electrochemical detection

5-HT :

5-hydroxytryptamine (serotonin)

NE :

norepinephrine

PD :

Parkinson's disease

PD-LT :

Parkinson's disease patients taking L-DOPA therapy

PD-LW :

Parkinson's disease patients withdrawn from L-DOPA therapy for 5 days

5-S-CyS-DA :

5-S-cysteinyldopamine

5-S-Glu-DA :

5-S-glutathionyldopamine

SN :

substantia nigra

O 2·:

Superoxide radical anion

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Author notes

  1. L. -G. Chia

    Present address: Section of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China

Authors and Affiliations

  1. Department of Medical Research and Geriatrics Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China

    F. -C. Cheng & J. -S. Kuo

  2. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA

    G. Dryhurst

Authors
  1. F. -C. Cheng
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  2. J. -S. Kuo
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  3. L. -G. Chia
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  4. G. Dryhurst
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Cheng, F.C., Kuo, J.S., Chia, L.G. et al. Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson's disease. J. Neural Transmission 103, 433–446 (1996). https://doi.org/10.1007/BF01276419

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  • DOI: https://doi.org/10.1007/BF01276419

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