Distribution of Na/K-ATPase Alpha 3 Isoform, a Sodium-Potassium P-Type Pump Associated With Rapid-Onset of Dystonia Parkinsonism (RDP) in the Adult Mouse Brain
Distribution of Na/K-ATPase Alpha 3 Isoform, a Sodium-Potassium P-Type Pump Associated With Rapid-Onset of Dystonia Parkinsonism (RDP) in the Adult Mouse Brain
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DOI：
10.1002/cne.22524
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发表时间：
2011-02-01
影响因子：
2.5
通讯作者：
Lykke-Hartmann, Karin
中科院分区：
文献类型：
--
作者：
Bottger, Pernille;Tracz, Zuzanna;Lykke-Hartmann, Karin
Na+/K+-ATP酶1 α亚基3（ATP 1 α（3））是维持动物细胞质膜钠和钾梯度的许多基本组分之一。ATP 1A 3基因的突变会导致肌张力障碍性帕金森综合征（RDP）的快速发作，这是一种罕见的运动障碍，其特征是肌张力障碍性痉挛的突然发作和运动缓慢。为了更好地理解这种疾病的病理生理学，我们使用免疫组织化学方法来描述ATP 1 α（3）在成年小鼠脑中的区域和细胞分布。我们的研究结果表明，ATP 1 α（3）的定位仅限于神经元，它主要表达在突起（纤维和标点），但也观察到胞体表达。我们发现ATP 1 α 3在基底神经节（纹状体、苍白球、丘脑底核和黑质）的所有核团中的GABA能神经元中都有高表达，这是精细运动控制的关键回路。几个丘脑核团的结构，窝藏连接和从皮质表达高水平的ATP 1 α（3）亚型。其他ATP 1 α（3）高表达的结构包括小脑、红核和脑桥的几个区域（脑桥网状被盖核）。我们还发现ATP 1 α（3）在海马的突起和胞体中有高表达，这些ATP 1 α（3）阳性胞体大多数与GABA能神经元共定位。黑质多巴胺能细胞ATP 1 α 3表达不明显。总之，根据我们的数据，ATP 1 α（3）在神经元群体中广泛表达，但主要在与运动控制相关的区域和核团中的GABA能神经元中表达，与RDP症状一致。J. Comp.神经元519：376-404，2011。(C)2010 Wiley-Liss，Inc.
The Na+/K+-ATPase1 alpha subunit 3 (ATP1 alpha(3)) is one of many essential components that maintain the sodium and potassium gradients across the plasma membrane in animal cells. Mutations in the ATP1A3 gene cause rapid-onset of dystonia parkinsonism (RDP), a rare movement disorder characterized by sudden onset of dystonic spasms and slowness of movement. To achieve a better understanding of the pathophysiology of the disease, we used immunohistochemical approaches to describe the regional and cellular distribution of ATP1 alpha(3) in the adult mouse brain. Our results show that localization of ATP1 alpha(3) is restricted to neurons, and it is expressed mostly in projections (fibers and punctuates), but cell body expression is also observed. We found high expression of ATP1 alpha(3) in GABAergic neurons in all nuclei of the basal ganglia (striatum, globus pallidus, subthalamic nucleus, and substantia nigra), which is a key circuitry in the fine movement control. Several thalamic nuclei structures harboring connections to and from the cortex expressed high levels of the ATP1 alpha(3) isoform. Other structures with high expression of ATP1 alpha(3) included cerebellum, red nucleus, and several areas of the pons (reticulotegmental nucleus of pons). We also found high expression of ATP1 alpha(3) in projections and cell bodies in hippocampus; most of these ATP1 alpha(3)-positive cell bodies showed colocalization to GABAergic neurons. ATP1 alpha(3) expression was not significant in the dopaminergic cells of substantia nigra. In conclusion, and based on our data, ATP1 alpha(3) is widely expressed in neuronal populations but mainly in GABAergic neurons in areas and nuclei related to movement control, in agreement with RDP symptoms. J. Comp. Neurol. 519:376-404, 2011. (C) 2010 Wiley-Liss, Inc.