Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy

Abstract Background Severe putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cys...

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Bibliographic Details
Published in:Parkinsonism & related disorders 2017-02, Vol.35, p.88-91
Main Authors: Goldstein, David S, Sullivan, Patti, Holmes, Courtney, Mash, Deborah C, Kopin, Irwin J, Sharabi, Yehonatan
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Cysteinyl-DOPA
Cysteinyl-dopamine
Denervation - trends
Dopamine - metabolism
Female
Humans
Male
Middle Aged
Multiple system atrophy
Multiple System Atrophy - metabolism
Multiple System Atrophy - pathology
Neurology
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson’s disease
Putamen - metabolism
Putamen - pathology
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Summary:Abstract Background Severe putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA. Methods Post-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA). Results The PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p 
ISSN:1353-8020
1873-5126
1873-5126
DOI:10.1016/j.parkreldis.2016.12.011