Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo 1 H-MRS study of an animal model for Parkinson's disease Chi-Bong Choi a , Sang-Young Kim b,c , Sung-Ho Lee d , Geon-Ho Jahng e , Hwi-Yool Kim d , Bo-Young Choe b,c , Kyung-Nam Ryu a , Dal-Mo Yang e , Sung-Vin Yim f , Woo-Suk Choi a, ⁎ a Department of Radiology, Kyung Hee University Medical Center, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea b Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul 137-040, Republic of Korea c Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul 137-040, Korea d Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea e Department of Radiology, East-West Neo Medical Center, School of Medicine, Kyung Hee University, Seoul 134-090, Republic of Korea f Department of Clinical Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea Received 20 July 2009; revised 29 December 2009; accepted 11 March 2010 Abstract 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 1 H water suppressed magnetic resonance spectroscopy ( 1 H-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 cm 3 ) 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 1 H-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. © 2011 Elsevier Inc. All rights reserved. Keywords: Parkinson's disease; Striatum; 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine; 1 H-MRS; Canine model 1. Introduction Parkinson's disease (PD) is a neurodegenerative disease of the central nerve system characterized by muscle rigidity, tremor, a slowing physical movement (bradykine- sia), and in extreme cases, accompanying a loss of physical movement (akinesia). The etiology of PD has not been clearly understood even though many genetic mutations associated with PD have been discovered [1–3]. There is also evidence mounting for the decreased activity of the mitochondrial respiratory complex І in substantia nigra, skeletal muscle and platelets playing an important role in its pathogenesis [4–6]. Inadvertent injection of 1-methyl-4-phenyl-1,2,3,6-tetra- hydropyridine (MPTP) induces progressive degeneration of dopaminergic neurons in the substantia nigra and concom- itant loss of dopamine in the striatum because the striatum receives its dopaminergic input from neurons of the substantia nigra pars compacta via nigrostriatal pathway [7]. After administration, MPTP crosses the blood-brain barrier and metabolizes in astrocytes to its active metabolite, 1-methyl-4-phenylpyridinium (MPP+), by monoamine oxi- dase-B [8,9]. MPP+ is selectively taken up into dopaminer- gic neurons via its affinity for the dopamine transporter, and thus selectively toxic to dopamine neurons [10]. MPP+ toxicity is believed to result from the inhibition of complex І Available online at www.sciencedirect.com Magnetic Resonance Imaging 29 (2011) 32 – 39 ⁎ Corresponding author. Tel.: +82 2 958 8614; fax: +82 2 968 0787. E-mail address: tomchoi100@khu.ac.kr (W.-S. Choi). 0730-725X/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2010.03.043