Assessment of metabolic changes in the striatum of a rat model of parkinsonism: an in vivo (1)H MRS study.

Degeneration of the dopaminergic neurons of the substantia nigra pars compacta in Parkinson's disease induces an abnormal activation of the glutamatergic neurotransmission system within the basal ganglia network and related structures. The aim of this study was to use proton MRS to show metabolic changes in the striatum of 6-hydroxydopamine-lesioned rats, a rodent animal model of Parkinson's disease. Animals were examined before and after extensive lesioning of the nigral dopaminergic neurons and after acute administration of L-3,4-dihydroxyphenylalanine. No significant alterations in glutamate concentrations, assessed by the MR signal dominated by glutamate with minor contributions from glutamine and gamma-aminobutyric acid, could be measured. The total choline/total creatine ratio was found to be reduced in the striatum of the ipsilateral hemisphere.

Kickler N ，Lacombe E ，Chassain C ，Durif F ，Krainik A ，Farion R ，Provent P ，Segebarth C ，Rémy C ，Savasta M ... -  《NMR IN BIOMEDICINE》

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.

Chassain C ，Bielicki G ，Durand E ，Lolignier S ，Essafi F ，Traoré A ，Durif F ... -  《-》

Glutamate measurement in Parkinson's disease using MRS at 3 T field strength.

Kickler N ，Krack P ，Fraix V ，Lebas JF ，Lamalle L ，Durif F ，Krainik A ，Rémy C ，Segebarth C ，Pollak P ... -  《-》

Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication.

Choi CB ，Kim SY ，Lee SH ，Jahng GH ，Kim HY ，Choe BY ，Ryu KN ，Yang DM ，Yim SV ，Choi WS ... -  《-》

Downregulation of glial glutamate transporters after dopamine denervation in the striatum of 6-hydroxydopamine-lesioned rats.

Overactivity of glutamatergic neurotransmission in the basal ganglia is known to be closely related to the onset and pathogenesis of Parkinson's disease. Glutamate homeostasis around glutamatergic synapses is tightly regulated by two groups of glutamate transporters: glial glutamate transporters GLT1 (EAAT2) and GLAST (EAAT1), and neuronal glutamate transporter EAAC1. In order to investigate the changes of glutamate transporters after the onset of Parkinson's disease, unilateral 6-hydroxydopamine-lesioned rat, an animal model of Parkinson's disease, was employed. By immunofluorescence and Western blot analyses, GLT1 and GLAST proteins were significantly reduced in the striatum with lesion. No change in GLT1 and GLAST protein was found in the substantia nigra. The reduction of GLT1 protein in the striatum was more prominent than that of GLAST protein (approximately 40% vs. 20%). In addition, EAAC1 protein was found to be increased in the substantia nigra pars reticulata of the lesioned rats but not in the striatum. The present results indicate that reductions of GLT1 and GLAST may impair glutamate homeostasis around glutamatergic synapses in the striatum and contribute to over-spills of glutamate in the system. An increase in the EAAC1 level in the substantia nigra pars reticulata may increase GABA synthesis and enhance GABAergic neurotransmission. These results indicate that there are differential and distinct modulations of glutamate transporters after dopamine denervation in the 6-hydroxydopamine-lesioned rat.

Chung EK ，Chen LW ，Chan YS ，Yung KK ... -  《-》