Changes in the rates of the tricarboxylic acid (TCA) cycle and glutamine synthesis in the monkey brain with hemiparkinsonism induced by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): studies by non-invasive 13C-magnetic resonance spectroscopy.

The tricarboxylic acid cycle rate (Vtca) and the rate of glutamine synthesis (Vgln) in the pre- and post-MPTP-treated cynomolgus monkey (Macaca fascicularis) brain were measured non-invasively using a 2 Tesla 13C-magnetic resonance spectroscopy (13C-MRS; multislice 1H-13C correlation heteronuclear single quantum coherence spectroscopy) system. Before the infusion of 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) into three monkeys, spectra were obtained by 13C-MRS from each monkey under anesthesia after the bolus injection of [1-13C] glucose (99% atom excess, 0.28 g/kg) followed by the continuous infusion of [1-13C] glucose (99% atom excess, 0.72 g/kg) into the saphenous vein for 3 h. The average values of Vtca were 0.475+/-0.077 (mean+/-S.D.) and 0.472+/-0.073 micromol/g/min, and the average values of Vgln were 0.042+/-0.007 and 0.041+/-0.008 mumol/g/min on the left and on the right hemisphere, respectively. Three monkeys were induced hemiparkinsonism by intracarotid (left) infusion of MPTP (0.6 mg/kg) and then were employed in 13C-MRS studies for 2 (5, 14 days), 3 (3, 8, 71 days) or 4 (5, 11, 27, 78 days) times, respectively, after the MPTP treatment. The average ratios of Vtca and Vgln on the left hemisphere to those on the right hemisphere in pre- and post-MPTP-treated monkeys were 0.837+/-0.085 and 1.373+/-0.132, respectively. These results of non-invasive 13C-MRS analysis of the MPTP primate model of Parkinson's disease indicate that the loss of the dopaminergic innervation from the caudate putamen may modulate the overall glucose metabolism to glutamate and glutamine in the ipsilateral cerebrum.

Carbon 13-labeled magnetic resonance spectroscopy observation of cerebral glucose metabolism: metabolism in MELAS: case report.

BACKGROUND: Carbon 13-labeled magnetic resonance spectroscopy ((13)C-MRS) with [(1-13)C]-glucose administration, the (13)C atom that behaves as a radio inactive tracer in the brain, can differentiate aerobic and anaerobic glucose metabolism by detecting [(4-13)C]-glutamate (Glu C4) and [(3-13)C]-lactate (Lac C3). OBJECTIVE: To investigate the cerebral metabolic derangement resulting from mitochondrial dysfunction in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). DESIGN: Application of a new (13)C-MRS technique to a patient with MELAS compared with control subjects (n = 7). PATIENT: A 19-year-old woman with an A3243G mitochondrial mutation who underwent (13)C-MRS for 30 minutes after oral administration of [(1-13)C]-glucose (0.75 g/kg). RESULT: Decreased Glu C4-labeling (P<.001) and increased Lac C3 synthesis (>2 SDs) compared with controls were demonstrated in the patient with MELAS. CONCLUSIONS: This first report on (13)C-MRS observation of cerebral glucose metabolism in a patient with MELAS demonstrated the presence of low glutamate production via the tricarboxylic acid cycle compared with high lactate synthesis by glycolysis. The present findings suggest that the clinical use of (13)C-MRS can be extended to diagnose mitochondrial dysfunction and monitor cerebral glucose metabolism in a variety of mitochondrial disorders.

Glutamate metabolism in epilepsy: 13C-magnetic resonance spectroscopy observation in the human brain.

To clarify changes in glutamate metabolism in the brain with chronic epileptic activities, 13C-magnetic resonance spectroscopy observation of glutamate and glutamine synthesis after oral administration of [1-13C] glucose (Glc C1) (0.75 g/kg) was performed in intractable occipital lobe epilepsy patients (n=5) and controls (n=10). 1H[13C]-spectra were obtained from two voxels of 64 ml placed on the bilateral parieto-occipital lobes of the study participants. Time courses for 13C-incorporation into 4-glutamate and 3-glutamate (Glu C4, C3) and 4-glutamine (Gln C4) were obtained and the concentrations of Glu C4, C3 and Gln C4 at the time between 120 and 150 min after Glc C1 administration was calculated. Concentration of Gln C4 was increased in the epilepsy patients [control: 0.39 mM (SD 0.14), epilepsy: 0.60 mM (SD 0.15), P<0.05], whereas those of Glu C4 and Glu C3 were not. The present study revealed increased glutamine synthesis compared with glutamate formation in a widespread cortical area with sustained epileptiform activities, possibly a result of chronic excessive glutamate release from neurons and subsequent uptake into astrocytes.

Mosaic Expression of the Reeler and Normal Phenotypes in the Cerebral Cortex in Reeler-Normal Chimeras at a Late Embryonic Stage: (reeler mutant mouse/mouse chimera/cerebral cortex/radial bundle/matrix cell).

The cerebral cortex of reeler-normal chimera embryos was studied by hematoxylin-eosin staining and fractographic scanning electron microscopy in comparison with the cortices of normal and reeler mutant mice. The cerebral cortex of normal mice had a plexiform layer, which was composed of a fine meshwork of matrix cell processes. Spindle shaped neuroblasts formed a radial lining columnar structure, which was formed by attachment of migrating neuroblasts to the radial bundles. The cerebral cortex of reeler mutants did not show a plexiform layer and the cells were round with no radially columnar structures, and no radial bundles. In reeler-normal chimera embryos, the thickness of the plexiform layer varied in different parts of the cerebral cortex. In parts where the plexiform layer was present, neuroblasts were spindle-shaped and had a radially oriented columnar structure (normal type). But where the plexiform layer was absent, the neuroblasts were round with a radial architecture (reeler type). Intermediates between the reeler and control types were also observed. Since mosaic expression of the two phenotypes, was observed in chimeras, the reeler abnormality is apparently not caused by humoral factors. The possible mechanism of cell migration is discussed.