In vivo imaging reveals impaired connectivity across cortical and subcortical networks in a mouse model of DYT1 dystonia.
In vivo imaging reveals impaired connectivity across cortical and subcortical networks in a mouse model of DYT1 dystonia.
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DOI：
10.1016/j.nbd.2016.07.005
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发表时间：
2016-11
影响因子：
6.1
通讯作者：
Vaillancourt, David E.
中科院分区：
文献类型：
--
作者：
DeSimone, Jesse C.;Febo, Marcelo;Shukla, Priyank;Ofori, Edward;Colon-Perez, Luis M.;Li, Yuqing;Vaillancourt, David E.
在Dyt 1 ΔGAG杂合基因敲入（Dyt 1 KI）小鼠中开发体内功能和结构神经成像试验，可深入了解Dyt 1肌张力障碍的病理生理学。在目前的研究中，我们研究了在体内的功能连接的大规模皮质和皮质下的网络在Dyt 1 KI小鼠和野生型（WT）的控制，使用静息态功能磁共振成像（MRI）和独立成分分析。此外，使用扩散MRI，我们研究了基底神经节和小脑的结构完整性如何直接与功能连接的损伤相关。与WT小鼠相比，Dyt 1 KI小鼠显示纹状体、丘脑和体感皮质的功能连接增加;运动和小脑皮质的功能连接减少。此外，与WT小鼠相比，Dyt 1 KI小鼠纹状体和小脑中的游离水（FW）升高，FW增加与基底神经节、小脑和感觉运动皮质的功能连接受损相关。目前的研究提供了第一个基于体内MRI的证据，支持以下假设：编码torsinA的Dyt 1基因中的3个碱基对（ΔGAG）序列的缺失对感觉运动皮层、基底神经节和小脑的体内功能连接和微结构完整性具有网络水平的影响。
Developing in vivo functional and structural neuroimaging assays in Dyt1 ΔGAG heterozygous knock-in (Dyt1 KI) mice provide insight into the pathophysiology underlying DYT1 dystonia. In the current study, we examined in vivo functional connectivity of large-scale cortical and subcortical networks in Dyt1 KI mice and wild-type (WT) controls using resting-state functional magnetic resonance imaging (MRI) and an independent component analysis. In addition, using diffusion MRI we examined how structural integrity across the basal ganglia and cerebellum directly relates to impairments in functional connectivity. Compared to WT mice, Dyt1 KI mice revealed increased functional connectivity across the striatum, thalamus, and somatosensory cortex; and reduced functional connectivity in the motor and cerebellar cortices. Further, Dyt1 KI mice demonstrated elevated free-water (FW) in the striatum and cerebellum compared to WT mice, and increased FW was correlated with impairments in functional connectivity across basal ganglia, cerebellum, and sensorimotor cortex. The current study provides the first in vivo MRI-based evidence in support of the hypothesis that the deletion of a 3-base pair (ΔGAG) sequence in the Dyt1 gene encoding torsinA has network level effects on in vivo functional connectivity and microstructural integrity across the sensorimotor cortex, basal ganglia, and cerebellum.
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影响因子：
8.6
作者：
Albanese, Alberto;Bhatia, Kailash;Bressman, Susan B.;DeLong, Mahlon R.;Fahn, Stanley;Fung, Victor S. C.;Hallett, Mark;Jankovic, Joseph;Jinnah, Hyder A.;Klein, Christine;Lang, Anthony E.;Mink, Jonathan W.;Teller, Jan K.
通讯作者：
Teller, Jan K.
影响因子：
5.3
作者：
Campbell, DB;North, JB;Hess, EJ
通讯作者：
Hess, EJ
影响因子：
17.6
作者：
Calhoun VD;Adalı T
通讯作者：
Adalı T
影响因子：
5.8
作者：
Bostan, Andreea C.;Strick, Peter L.
通讯作者：
Strick, Peter L.
影响因子：
8.6
作者：
Carbon, Maren;Kingsley, Peter B.;Eidelberg, David
通讯作者：
Eidelberg, David