Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Jeong, Hyeonseok S.; Im, Jooyeon J.; Chung, Yong-An] Catholic Univ Korea, Incheon St Marys Hosp, Dept Radiol, Coll Med, Seoul, South Korea; [Lee, Sang-Rae; Chang, Kyu-Tae] Korean Res Inst Biosci & Biotechnol, Natl Primate Res Ctr, Ochang, South Korea; [Kim, Jieun E.; Lyoo, In Kyoon; Yoon, Sujung; Namgung, Eun; Im, Jooyeon J.; Jeon, Saerom; Kang, Ilhyang; Ma, Jiyoung] Ewha Womans Univ, Ewha Brain Inst, Seoul, South Korea; [Kim, Jieun E.; Lyoo, In Kyoon; Yoon, Sujung; Namgung, Eun; Jeon, Saerom; Kang, Ilhyang; Lim, Soo Mee] Ewha Womans Univ, Dept Brain & Cognit Sci, Seoul, South Korea; [Lyoo, In Kyoon] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul, South Korea; [Kim, Bom Sahn] Ewha Womans Univ, Dept Nucl Med, Mokdong Hosp, Seoul, South Korea; [Yang, Sejung] Ewha Womans Univ, Inst Convergence Med, Med Ctr, Seoul, South Korea; [Im, Jooyeon J.; Ma, Jiyoung] Seoul Natl Univ, Coll Nat Sci, Interdisciplinary Program Neurosci, Seoul, South Korea; [Lim, Soo Mee] Ewha Womans Univ, Dept Radiol, Mokdong Hosp, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 PUBLIC LIBRARY SCIENCE
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000160200
- 본문언어 영어
- Published As http://dx.doi.org/10.1371/journal.pone.0189804
초록/요약
In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.
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