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

The Na + /K + ‐ATPase1 alpha subunit 3 (ATP1α 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 ATP1α 3 in the adult mouse brain. Our results show that localization of ATP1α 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 ATP1α 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 ATP1α 3 isoform. Other structures with high expression of ATP1α 3 included cerebellum, red nucleus, and several areas of the pons (reticulotegmental nucleus of pons). We also found high expression of ATP1α 3 in projections and cell bodies in hippocampus; most of these ATP1α 3 ‐positive cell bodies showed colocalization to GABAergic neurons. ATP1α 3 expression was not significant in the dopaminergic cells of substantia nigra. In conclusion, and based on our data, ATP1α 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. © 2010 Wiley‐Liss, Inc.