Parkinson壮s disease-related modulation of functional connectivity associated with the striatum in the resting state in a nonhuman primate model

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• 作者：Jianpeng Li^a ; Chunyan Luo^a ; Yongping Chen^a ; Qin Chen^a ; Rui Huang^a ; Jiayu Sun^b ; Qiyong Gong^b ; Xiaoai Wu^c ; Zhongzhi Qi^c ; Zhenglu Liang^c ; Lin Li^c ; Hongxia Li^d ; Peng Li^e ; Wei Wang^e ; Hui-Fang Shang^a ; ^{hfshang2002@163.com" class="auth_mail}
• 关键词：[18F] AV-133 ; 9-[18F] fluoropropyl-(+)-dihydrotetrabenazine ; ACC ; anterior cingulate cortex ; ANOVA ; analysis of variance ; BG ; basal ganglia ; CA ; caudate nucleus/associative ; CN ; caudate nucleus ; DLPFC ; dorsolateral prefrontal cortex ; FC ; functional connectivity ; fMRI ; functional magnetic resonance imaging ; ITG ; inferior temporal gyrus ; LS ; limbic striatum ; MEG ; magnetoencephalography ; MFG ; middle frontal gyrus ; MPTP ; 1-methyl-4-phenyl-1 ; 2 ; 3 ; 6- tetrahydropyridine ; OMPFC ; orbital and medial prefro
• 刊名：Brain Research
• 出版年：25 March, 2014
• 年：2014
• 卷：1555
• 期：Complete
• 页码：10-19
• 全文大小：1588 K

文摘

The goal of this study was to describe Parkinson壮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-[¹⁸F] 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.