Metabolic changes detected by proton magnetic resonance spectroscopy in vivo and in vitro in a murin model of Parkinson’s disease, the MPTP-intoxicated mouse - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Neurochemistry Année : 2008

Metabolic changes detected by proton magnetic resonance spectroscopy in vivo and in vitro in a murin model of Parkinson’s disease, the MPTP-intoxicated mouse

Carine Chassain
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Elodie Durand
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Stéphane Lolignier
Amidou Traore

Résumé

Parkinson'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 H-1 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 mu L) 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 H-1 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 mu mol/g, p < 0.05), Gln (6.8 +/- 2.9 vs. 4.3 +/- 1.0 mu mol/g, p < 0.05), and GABA (2.9 +/- 0.9 vs. 1.5 +/- 0.4 mu mol/g, p < 0.01). The present study strongly supports a hyperactivity of the glutamatergic cortico-striatal pathway hypothesis after dopaminergic denervation in association with an increase of striatal GABA levels. It further shows an increased of striatal Gln concentrations, perhaps as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion.

Dates et versions

hal-01602181 , version 1 (02-10-2017)

Identifiants

Citer

Carine Chassain, Guy Bielicki, Elodie Durand, Stéphane Lolignier, Fatma Essafi, et al.. Metabolic changes detected by proton magnetic resonance spectroscopy in vivo and in vitro in a murin model of Parkinson’s disease, the MPTP-intoxicated mouse. Journal of Neurochemistry, 2008, 105 (3), pp.874-882. ⟨10.1111/j.1471-4159.2007.05185.x⟩. ⟨hal-01602181⟩
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