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
Chi-Bong
CB
Department of Radiology, Kyung Hee University Medical Center, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
Kim
Sang-Young
SY
Lee
Sung-Ho
SH
Jahng
Geon-Ho
GH
Kim
Hwi-Yool
HY
Choe
Bo-Young
BY
Ryu
Kyung-Nam
KN
Yang
Dal-Mo
DM
Yim
Sung-Vin
SV
Choi
Woo-Suk
WS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D020267:MPTP Poisoning / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D014018:Tissue Distribution
D001224:Aspartic Acid; C000179:N-acetylaspartate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003401:Creatine; D002794:Choline