Wfs1-deficient animals have brain-region-specific changes of Na+, K+-ATPase activity and mRNA expression of α1 and β1 subunits.
Mutations in the WFS1 gene, which encodes the endoplasmic reticulum (ER) glycoprotein, cause Wolfram syndrome, a disease characterized by juvenile-onset diabetes mellitus, optic atrophy, deafness, and different psychiatric abnormalities. Loss of neuronal cells and pancreatic β-cells in Wolfram syndrome patients is probably related to the dysfunction of ER stress regulation, which leads to cell apoptosis. The present study shows that Wfs1-deficient mice have brain-region-specific changes in Na(+),K(+)-ATPase activity and in the expression of the α1 and β1 subunits. We found a significant (1.6-fold) increase of Na-pump activity and β1 subunit mRNA expression in mice lacking the Wfs1 gene in the temporal lobe compared with their wild-type littermates. By contrast, exposure of mice to the elevated plus maze (EPM) model of anxiety decreased Na-pump activity 1.3-fold in the midbrain and dorsal striatum and 2.0-fold in the ventral striatum of homozygous animals compared with the nonexposed group. Na-pump α1 -subunit mRNA was significantly decreased in the dorsal striatum and midbrain of Wfs1-deficient homozygous animals compared with wild-type littermates. In the temporal lobe, an increase in the activity of the Na-pump is probably related to increased anxiety established in Wfs1-deficient mice, whereas the blunted dopamine function in the forebrain of Wfs1-deficient mice may be associated with a decrease of Na-pump activity in the dorsal and ventral striatum and in the midbrain after exposure to the EPM.
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Centre of Excellence for Translational Medicine, Tartu, Estonia.
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Sütt
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Altpere
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Reimets
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Visnapuu
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Loomets
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Raud
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Salum
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Mahlapuu
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Kairane
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Zilmer
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Vasar
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; C114987:wolframin protein; D000254:Sodium-Potassium-Exchanging ATPase
Na-pump; anxiety; elevated plus-maze; gene expression