Dopamine reduction in the substantia nigra of Parkinson's disease patients confirmed by in vivo magnetic resonance spectroscopic imaging.

<h4>Objectives</h4>Metabolic changes in the substantia nigra of patients with Parkinson's disease were previously investigated in different molecular-pathological examinations. The aim of our study was the in vivo measurement of these alterations using three-dimensional magnetic res...

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Autores principales: Adriane Gröger, Rupert Kolb, Rita Schäfer, Uwe Klose
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/3a8ed90ca6314fb193729682521030a2
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Sumario:<h4>Objectives</h4>Metabolic changes in the substantia nigra of patients with Parkinson's disease were previously investigated in different molecular-pathological examinations. The aim of our study was the in vivo measurement of these alterations using three-dimensional magnetic resonance spectroscopic imaging.<h4>Methods</h4>21 patients with Parkinson's disease and 24 controls were examined using magnetic resonance spectroscopic imaging at 3 Tesla. The spectra of rostral and caudal substantia nigra regions were analyzed using LCModel. For spectral fitting, an adjusted basis data set with pathology-specific metabolites and macromolecules was used to better reproduce the in vivo spectra. To assess differences between both groups more accurately, especially in metabolites at lower concentrations, group-averaged spectra were evaluated in addition to the analysis of individual data.<h4>Results</h4>We found significantly decreased N-acetylaspartate, choline, creatine, myo-inositol, glutathione and dopamine concentrations in patients with Parkinson's disease compared to controls, whereas glutamine+glutamate, γ-aminobutyric acid, and homovanillic acid were slightly increased. According to anatomical features, clear differences in the biochemical profiles were found between rostral and caudal substantia nigra voxels in both groups.<h4>Conclusions</h4>Reduced N-acetylaspartate and dopamine concentrations result from progressive degeneration of dopamine-producing neurons within the substantia nigra pars compacta. Decreased creatine levels can be interpreted as impaired energy metabolism due to mitochondrial dysfunction. Lower glutathione concentrations might be a cause or consequence of oxidative stress. Furthermore, slightly increased glutamine+glutamate and γ-aminobutyric acid levels are expected based on post mortem data in Parkinson's disease. To the best of our knowledge, this is the first non-invasive confirmation of these metabolic changes.