title: Neurometabolic profiles of the substantia nigra and striatum of MPTP-intoxicated common marmosets: An in vivo proton MRS study at 9.4 T.
abstract: Given the strong coupling between the substantia nigra (SN) and striatum (STR) in the early stage of Parkinson's disease (PD), yet only a few studies reported to date that have simultaneously investigated the neurochemistry of these two brain regions in vivo, we performed longitudinal metabolic profiling in the SN and STR of 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated common marmoset monkey models of PD (n = 10) by using proton MRS (1H-MRS) at 9.4 T. T2relaxometry was also performed in the SN by using MRI. Data were classified into control, MPTP_2weeks, and MPTP_6-10 weeks groups according to the treatment duration. In the SN, T2of the MPTP_6-10 weeks group was lower than that of the control group (44.33 ± 1.75 versus 47.21 ± 2.47 ms, p < 0.05). The N-acetylaspartate to total creatine ratio (NAA/tCr) and γ-aminobutyric acid to tCr ratio (GABA/tCr) of the MPTP_6-10 weeks group were lower than those of the control group (0.41 ± 0.04 versus 0.54 ± 0.08 (p < 0.01) and 0.19 ± 0.03 versus 0.30 ± 0.09 (p < 0.05), respectively). The glutathione to tCr ratio (GSH/tCr) was correlated with T2for the MPTP_6-10 weeks group (r = 0.83, p = 0.04). In the STR, however, GABA/tCr of the MPTP_6-10 weeks group was higher than that of the control group (0.25 ± 0.10 versus 0.16 ± 0.05, p < 0.05). These findings may be an in vivo depiction of the altered basal ganglion circuit in PD brain resulting from the degeneration of nigral dopaminergic neurons and disruption of nigrostriatal dopaminergic projections. Given the important role of non-human primates in translational studies, our findings provide better understanding of the complicated evolution of PD.
authors.affiliation: Department of Biomedical Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Hwon
authors.initials: H
authors.lastname: Heo
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Hyeong Hun
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Euna
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Biomedical Sciences, Seoul National University, Seoul, South Korea.|Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Department of Radiology, Seoul National University Hospital, Seoul, South Korea.|Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea.
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea.|Designed Animal and Transplantation Research Institute, Institute of GreenBio Science and Technology, Seoul National University, Pyeongchang, South Korea.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Kang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002144:Callithrix; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D057054:Molecular Imaging / Q000379:methods; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D010363:Pattern Recognition, Automated / Q000379:methods*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: 1-methyl-1,2,3,6-tetrahydropyridine; MRS; Parkinson's disease; common marmoset; striatum; substantia nigra