title: Parkinson׳s disease-related modulation of functional connectivity associated with the striatum in the resting state in a nonhuman primate model.
abstract: The goal of this study was to describe Parkinson׳s disease (PD)-related modulation of functional connectivity (FC) associated with the striatum in the resting state in a nonhuman primate model of early-stage PD. Weekly intravenous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (0.5 mg/kg body weight) were performed until parkinsonian motor symptoms developed in four macaques. After 13 weeks of MPTP treatment, all monkeys displayed parkinsonian symptoms. During the course of the experiment, each animal underwent four magnetic resonance imaging scans and four positron emission tomography (PET) scans with the vesicular monoamine transporter 2 (VMAT2)-selective ligand 9-[(18)F] fluoropropyl-(+)-dihydrotetrabenazine, performed prior to the beginning of MPTP administration as well as after 4, 9, and 13 MPTP injections. The FC profile of the striatum was evaluated using a seed voxel correlation approach and post hoc region of interest analysis on resting-state functional magnetic resonance imaging data. The PET images were subjected to region of interest analysis to examine brain regional reductions in VMAT2 density in the PD model. Significant reductions in the connectivity pattern of the striatal regions were observed: limbic striatum and left hippocampus; caudate nucleus/associative and brain regions, including the right pre-supplementary motor area and bilateral dorsolateral prefrontal cortex; putamen/associative region and left inferior temporal gyrus or right orbital and medial prefrontal cortex; and putamen/motor and cortical structures, including the right superior temporal gyrus and bilateral postcentral gyrus. Subsequent PET studies showed the progressive loss of striatal VMAT2 in the striatum with the presentation of parkinsonism. Significant differences between the specific uptake ratio reductions in each striatal subdivision were not found. By using a long-term, low-dose MPTP-lesioned nonhuman primate model, this study demonstrated PD-related decreased corticostriatal FC in a resting state; moreover, altered sensorimotor integration was also found in early-stage PD.
authors: Department of Neurology, West China Hospital, Sichuan University, China.
authors: Jianpeng
authors: J
authors: Li
authors: Department of Neurology, West China Hospital, Sichuan University, China.
authors: Chunyan
authors: C
authors: Luo
authors: Department of Neurology, West China Hospital, Sichuan University, China.
authors: Yongping
authors: Y
authors: Chen
authors: Department of Neurology, West China Hospital, Sichuan University, China.
authors: Qin
authors: Q
authors: Chen
authors: Department of Neurology, West China Hospital, Sichuan University, China.
authors: Rui
authors: R
authors: Huang
authors: Department of Radiology, West China Hospital, Sichuan University, China.
authors: Jiayu
authors: J
authors: Sun
authors: Department of Radiology, West China Hospital, Sichuan University, China.
authors: Qiyong
authors: Q
authors: Gong
authors: Department of Nuclear Medicine, West China Hospital, Sichuan University, China.
authors: Xiaoai
authors: X
authors: Wu
authors: Department of Nuclear Medicine, West China Hospital, Sichuan University, China.
authors: Zhongzhi
authors: Z
authors: Qi
authors: Department of Nuclear Medicine, West China Hospital, Sichuan University, China.
authors: Zhenglu
authors: Z
authors: Liang
authors: Department of Nuclear Medicine, West China Hospital, Sichuan University, China.
authors: Lin
authors: L
authors: Li
authors: National Chengdu Center for Safety Evaluation of Drugs, China.
authors: Hongxia
authors: H
authors: Li
authors: Department of Neurosurgery, West China Hospital, Sichuan University, China.
authors: Peng
authors: P
authors: Li
authors: Department of Neurosurgery, West China Hospital, Sichuan University, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurology, West China Hospital, Sichuan University, China. Electronic address: hfshang2002@163.com.
authors: Hui-Fang
authors: HF
authors: Shang
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D020267:MPTP Poisoning / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D049268:Positron-Emission Tomography
keywords: MPTP; Non-human primates; PD; PET; Resting-state fMRI