Dopamine Reduction in the Substantia Nigra of Parkinson's Disease Patients Confirmed by In Vivo Magnetic Resonance Spectroscopic Imaging

Abstract

ObjectivesMetabolic 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.Methods21 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.ResultsWe 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.ConclusionsReduced 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.

Bereitschaftspotential preceding eyelid blinks in Parkinson’s disease

“…Nondopaminergic pathways play a role in the clinical improvement of motor planning and BP amplitude in PD patients, as observed after unilateral posteroventral pallidotomy 28 and after neurofeedback techniques 25 . These studies corroborate the presence and importance of nondopaminergic or dopaminergic pathways resistant to modulation mechanisms of the motor planning in PD 6 . The amplitudes at C3, Cz and C4 were not significantly different in PD patients.…”

“…Voids in the dopaminergic and nondopaminergic circuits have been involved in this pathophysiology, generating an imbalance between inhibition and excitation, deficits and compensation 4,5,6 . Changes in the dopaminergic pathways explain, at least in part, disturbances in the kinematics of spontaneous eyelid blink 7,8,9 , and the voluntary one 10 and in the blink reflex habituation of PD…”

Nutritional Supplementation, Diet, and Genetics and Their Impact on Parkinson’s Disease (PD), a Review of Studies

“…The modified GSH/GSSG ratio in the substantia nigra observed in PD is consistent with findings that have shown oxidative stress being a major component in the pathogenesis of nigral cell death in PD. 33 A study conducted by Groger et al, 34 investigated dopamine reduction in the substantia nigra of PD patients using in vivo magnetic resonance spectroscopic imaging. The study sought to confirm metabolic changes in the substantia nigra of PD patients which had traditionally been investigated using different molecularpathological examinations.…”

“…The lower levels of glutathione were interpreted as a result of oxidative stress. 34 A study was conducted by Elokda et al, 35 to establish the effects of exercise induced oxidative stress on glutathione levels in Parkinson's disease during off and on medication. The study was conducted on the findings that show resting plasma GSH levels to be lower in people suffering from PD in comparison to other neurological conditions.…”

Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning

“…(Burns et al 1983;Chinta and Andersen 2005;Groger et al 2014). Actually, SN consists of three diff erent parts, pars compacta, pars reticulata, and pars lateralis (Dahlstrom and Fuxe 1964).…”