Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.

Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by st...

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Main Authors: Uzay E Emir, Paul J Tuite, Gülin Öz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3266292?pdf=render
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author Uzay E Emir
Paul J Tuite
Gülin Öz
author_facet Uzay E Emir
Paul J Tuite
Gülin Öz
author_sort Uzay E Emir
collection DOAJ
description Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown.To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. γ-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p<0.001 for pons and p<0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls.The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of the lower brainstem. This study provides in vivo evidence for an alteration in the GABAergic tone in the lower brainstem and striatum in early-moderate PD, which may underlie disease pathogenesis and may provide a biomarker for disease staging.
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spelling doaj.art-ba2cf1d52900442b9e316b0abc3e130d2022-12-21T19:34:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e3091810.1371/journal.pone.0030918Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.Uzay E EmirPaul J TuiteGülin ÖzParkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown.To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. γ-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p<0.001 for pons and p<0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls.The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of the lower brainstem. This study provides in vivo evidence for an alteration in the GABAergic tone in the lower brainstem and striatum in early-moderate PD, which may underlie disease pathogenesis and may provide a biomarker for disease staging.http://europepmc.org/articles/PMC3266292?pdf=render
spellingShingle Uzay E Emir
Paul J Tuite
Gülin Öz
Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
PLoS ONE
title Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
title_full Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
title_fullStr Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
title_full_unstemmed Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
title_short Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS.
title_sort elevated pontine and putamenal gaba levels in mild moderate parkinson disease detected by 7 tesla proton mrs
url http://europepmc.org/articles/PMC3266292?pdf=render
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