Heo Hwon, Ahn Jae-Bum, Lee Hyeong Hun, Kwon Euna, Yun Jun-Won, Kim Hyeonjin, Kang Byeong-Cheol
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.
NMR Biomed. 2017 Feb;30(2). doi: 10.1002/nbm.3686. Epub 2016 Dec 28.
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 ( H-MRS) at 9.4 T. T relaxometry 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, T of 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 T for 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.
鉴于帕金森病（PD）早期黑质（SN）和纹状体（STR）之间存在强耦合，然而迄今为止仅有少数研究报道在体内同时研究这两个脑区的神经化学，我们通过使用9.4T的质子磁共振波谱（H-MRS）对1-甲基-1,2,3,6-四氢吡啶（MPTP）诱导的PD普通狨猴模型（n = 10）的SN和STR进行了纵向代谢谱分析。还通过MRI在SN中进行了T2弛豫测量。根据治疗持续时间将数据分为对照组、MPTP_2周组和MPTP_6 - 10周组。在SN中，MPTP_6 - 10周组的T2低于对照组（44.33±1.75对47.21±2.47毫秒，p < 0.05）。MPTP_6 - 10周组的N-乙酰天门冬氨酸与总肌酸比值（NAA/tCr）和γ-氨基丁酸与tCr比值（GABA/tCr）低于对照组（分别为0.41±0.04对0.54±0.08（p < 0.01）和0.19±0.03对0.30±0.09（p < 0.05））。MPTP_6 - 10周组的谷胱甘肽与tCr比值（GSH/tCr）与T2相关（r = 0.83，p = 0.04）。然而，在STR中，MPTP_6 - 10周组的GABA/tCr高于对照组（0.25±0.10对0.16±0.05，p < 0.05）。这些发现可能是PD脑中由于黑质多巴胺能神经元变性和黑质纹状体多巴胺能投射破坏导致的基底神经节回路改变的体内描述。鉴于非人灵长类动物在转化研究中的重要作用，我们的发现为更好地理解PD的复杂演变提供了依据。
