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.
Kanamatsu
Tomoyuki
T
Institute of Life Science, Soka University, 1-236 Tangi-machi, Hachioji-shi, Tokyo 192-8577, Japan. kanamatu@t.soka.ac.jp
Otsuki
Taisuke
T
Tokuno
Hironobu
H
Nambu
Atsusi
A
Takada
Masahiko
M
Okamoto
Kazuya
K
Watanabe
Hidehiro
H
Umeda
Masaaki
M
Tsukada
Yasuzo
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism*
D002247:Carbon Isotopes; D005973:Glutamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine