Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a severe loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and a concomitant decrease of dopamine (DA) in the striatum (Marsden 1994). The degeneration of nigrostriatal dopaminergic neurons causes dysfunction of the cortico-basal Received October 16, 2007; revised manuscript received December 3, 2007; accepted December 5, 2007. Address correspondence and reprint requests to Carine Chassain, INRA UR370 QuaPA/STIM, Clermont-Ferrand/Theix, 63122 Saint Genès Champanelle, France. E-mail: kchassin@sancy.clermont.inra.frAbbreviations used: BG, basal ganglia; DA, dopamine; GAD, glutamate decarboxylase; Gln, glutamine; Glu, glutamate; Glx, Glu + Gln; Lac, lactate; MRS, magnetic resonance spectroscopy; Myo-Ins, myoinositol; NAA, N-acetyl aspartate; PD, Parkinson's disease; PRESS, point-resolved spectroscopy; SNpc, substantia nigra pars compacta; Tau, taurine; TBS, Tris-buffered saline; tCho, total choline; tCr, total creatine; TH, tyrosine hydroxylase; TSP, 3-(trimethylsilyl)-propionic acid-D4, sodium salt; VOI, voxel of interest.
AbstractParkinson's disease is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which project to the striatum. The aim of this study was to analyze in vivo and in vitro consequences of dopamine depletion on amount of metabolites in a mouse model of Parkinson's disease using proton 1 H magnetic resonance spectroscopy (MRS). The study was performed on control mice (n = 7) and MPTP-intoxicated mice (n = 7). All the experiments were performed at 9.4 T. For in vivo MRS acquisitions, mice were anesthetized and carefully placed on an animal handling system with the head centered in birdcage coil used for both excitation and signal reception. Spectra were acquired in a voxel (8 lL) centered in the striatum, applying a point-resolved spectroscopy sequence (TR = 4000 ms, TE = 8.8 ms). After in vivo MRS acquisitions, mice were killed; successful lesion verified by tyrosine hydroxylase immunolabeling on the substantia nigra pars compacta and in vitro MRS acquisitions performed on perchloric extracts of anterior part of mice brains. In vitro spectra were acquired using a standard one-pulse experiment. The absolute concentrations of metabolites were determined using JMRUI (Lyon, France) from 1 H spectra obtained in vivo on striatum and in vitro on perchloric extracts. Glutamate (Glu), glutamine (Gln), and GABA concentrations obtained in vivo were significantly increased in striatum of MPTP-lesioned mice (Glu: 15.5 ± 2.5 vs. 12.9 ± 1.0 mmol/L, p < 0.05; Gln: 2.3 ± 0.9 vs. 1.8 ± 0.6 mmol/L, p < 0.05; GABA: 2.3 ± 0.9 vs. 1.3 ± 0.6 mmol/L, p < 0.05). The in vitro results confirmed these results, Glu (10.9 ± 2.5 vs. 7.9 ± 1.7 lmol/g, p < 0.05), Gln (6.8 ± 2.9 vs. 4.3 ± 1.0 lmol/g, p < 0.05), and GABA (2.9 ± 0.9 vs. 1.5 ± 0.4 lmol/g, p < 0.01). The present study strongly supports a hyperactivity of the glutamatergic cor...