Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS 英文参考文献.docVIP

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Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS 英文参考文献.doc

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Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS 英文参考文献

ElevatedPontineandPutamenalGABALevelsinMild- ModerateParkinsonDiseaseDetectedby7TeslaProton MRS UzayE.Emir1*,PaulJ.Tuite2,Gu¨linOz¨ 1 1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, United States of America, 2Department of Neurology,UniversityofMinnesota,Minneapolis,Minnesota,UnitedStatesofAmerica Abstract Background:Parkinsondisease(PD)ischaracterizedbythedegenerationofnigrostriataldopaminergicneurons.However, postmortemevidenceindicatesthatthepathologyoflowerbrainstemregions,suchastheponsandmedulla,precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. NeurochemicalcorrelatesofthisearlypathologicalinvolvementinPDareunknown. Methodology/Principal Finding: 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. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantlyhigherinpatients(N=11,offmedications)thancontrols(N=11,p,0.001forponsandp,0.05forputamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differenceswereobservedbetweenpatientsandcontrols. Conclusion/Significance:TheGABAelevationintheputamenisconsistentwithpriorpostmortemfindingsinpatientswith PD,aswellaswithinvivoobservationsinarodentmodelofPD,whiletheGABAfindingintheponsisnovel.Themore significantGABAelevationintheponsrelativetotheputamenisconsistentwithearlierpathologicalinvolvementofthe lowerbrainstem.ThisstudyprovidesinvivoevidenceforanalterationintheGABAergictoneinthelowerbrainstemand striatuminearly-moderatePD,whichmayunderliediseasepathogenesisandmayprovideabiomarkerfordiseas