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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

Title
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
Authors
Jeong, Hyeonseok S.Lee, Sang-RaeKim, Jieun E.Lyoo, In KyoonYoon, SujungNamgung, EunChang, Kyu-TaeKim, Bom SahnYang, SejungIm, Jooyeon J.Jeon, SaeromKang, IlhyangMa, JiyoungChung, Yong-AnLim, Soo Mee
Ewha Authors
임수미류인균양세정
SCOPUS Author ID
임수미scopus; 류인균scopus; 양세정scopus
Issue Date
2018
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 13, no. 1
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS
Abstract
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.
DOI
10.1371/journal.pone.0189804
Appears in Collections:
의과대학 > 의학과 > Journal papers
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