| First Author | Ikeda K | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 2 | Pages | e0246678 |
| PubMed ID | 33544780 | Mgi Jnum | J:302184 |
| Mgi Id | MGI:6506353 | Doi | 10.1371/journal.pone.0246678 |
| Citation | Ikeda K, et al. (2021) Decreased content of ascorbic acid (vitamin C) in the brain of knockout mouse models of Na+,K+-ATPase-related neurologic disorders. PLoS One 16(2):e0246678 |
| abstractText | Na+,K+-ATPase is a crucial protein responsible for maintaining the electrochemical gradients across the cell membrane. The Na+,K+-ATPase is comprised of catalytic alpha, beta, and gamma subunits. In adult brains, the alpha3 subunit, encoded by ATP1A3, is predominantly expressed in neurons, whereas the alpha2 subunit, encoded by ATP1A2, is expressed in glial cells. In foetal brains, the alpha2 is expressed in neurons as well. Mutations in alpha subunits cause a variety of neurologic disorders. Notably, the onset of symptoms in ATP1A2- and ATP1A3-related neurologic disorders is usually triggered by physiological or psychological stressors. To gain insight into the distinct roles of the alpha2 and alpha3 subunits in the developing foetal brain, whose developmental dysfunction may be a predisposing factor of neurologic disorders, we compared the phenotypes of mouse foetuses with double homozygous knockout of Atp1a2 and Atp1a3 (alpha2alpha3-dKO) to those with single knockout. The brain haemorrhage phenotype of alpha2alpha3-dKO was similar to that of homozygous knockout of the gene encoding ascorbic acid (ASC or vitamin C) transporter, SVCT2. The alpha2alpha3-dKO brain showed significantly decreased level of ASC compared with the wild-type (WT) and single knockout. We found that the ASC content in the basal ganglia and cerebellum was significantly lower in the adult Atp1a3 heterozygous knockout mouse (alpha3-HT) than in the WT. Interestingly, we observed a significant decrease in the ASC level in the basal ganglia and cerebellum of alpha3-HT in the peripartum period, during which mice are under physiological stress. These observations indicate that the alpha2 and alpha3 subunits independently contribute to the ASC level in the foetal brain and that the alpha3 subunit contributes to ASC transport in the adult basal ganglia and cerebellum. We propose that decreases in ASC levels may affect neural network development and are linked to the pathophysiology of ATP1A2- and ATP1A3-related neurologic disorders. |
