The DYT1 carrier state increases energy demand in the olivocerebellar network.
The DYT1 carrier state increases energy demand in the olivocerebellar network.
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DYT1 载体状态增加了橄榄小脑网络的能量需求。
DOI：
10.1016/j.neuroscience.2011.01.015
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发表时间：
2011
期刊：
影响因子：
3.3
通讯作者：
LeDoux,MS
中科院分区：
文献类型：
--
作者：
Zhao,Y;Sharma,N;LeDoux,MS
DYT1肌张力障碍是由编码torsinA的基因TOR1A的GAG缺失引起的。啮齿类动物的基因表达研究和人类的功能影像学研究表明，DYT1肌张力障碍可能是一种神经发育起源的网络障碍。为了生成DYT1肌张力障碍的高分辨率代谢图谱和精确定位失调的网络元件，我们对表达人类突变体（hMT1） torsinA的转基因小鼠和野生型幼崽进行了2-脱氧葡萄糖放射自显影和细胞色素氧化酶（CO）组织化学。与对照组相比，hMT1小鼠的下橄榄核（IO）内侧核（IOM）、IO背副核和紧黑质的葡萄糖利用率（GU）增加，内侧苍白球（MGP）和外侧苍白球的GU降低。hMT1小鼠小脑皮层IOM和浦肯野细胞层CO活性升高，尾状尾壳核、网状黑质和MGP CO活性降低。这些发现表明：(1)DYT1载体状态增加了脑小脑网络的能量需求；(2)IO可能是肌张力障碍中基底神经节-小脑相互作用异常的关键节点。
DYT1 dystonia is caused by a GAG deletion in TOR1A, the gene which encodes torsinA. Gene expression studies in rodents and functional imaging studies in humans suggest that DYT1 dystonia may be a network disorder of neurodevelopmental origin. To generate high resolution metabolic maps of DYT1 dystonia and pinpoint dysregulated network elements, we performed 2-deoxyglucose autoradiography and cytochrome oxidase (CO) histochemistry in transgenic mice expressing human mutant (hMT1) torsinA and wild-type littermates. In comparison with controls, hMT1 mice showed increased glucose utilization (GU) in the inferior olive (IO) medial nucleus (IOM), IO dorsal accessory nucleus and substantia nigra compacta, and decreased GU in the medial globus pallidus (MGP) and lateral globus pallidus. The hMT1 mice showed increased CO activity in the IOM and Purkinje cell layer of cerebellar cortex, and decreased CO activity in the caudal caudate-putamen, substantia nigra reticulata and MGP. These findings suggest that (1) the DYT1 carrier state increases energy demand in the olivocerebellar network and (2) the IO may be a pivotal node for abnormal basal ganglia-cerebellar interactions in dystonia.