| First Author | Sosnoski HM | Year | 2020 |
| Journal | Neurochem Int | Volume | 141 |
| Pages | 104888 | PubMed ID | 33199267 |
| Mgi Jnum | J:307540 | Mgi Id | MGI:6721180 |
| Doi | 10.1016/j.neuint.2020.104888 | Citation | Sosnoski HM, et al. (2020) Sexually dimorphic and brain region-specific transporter adaptations in system xc(-) null mice. Neurochem Int 141:104888 |
| abstractText | System xc(-) is a heterodimeric amino acid antiporter that, in the central nervous system, is best known for linking the import of L-cystine (CySS) with the export of L-glutamate for the production and maintenance of cellular glutathione (GSH) and extracellular glutamate levels, respectively. Yet, mice that are null for system xc(-) are healthy, fertile, and, morphologically, their brains are grossly normal. This suggests other glutamate and/or cyst(e)ine transport mechanisms may be upregulated in compensation. To test this, we measured the plasma membrane expression of Excitatory Amino Acid Transporters (EAATs) 1-3, the Alanine-Serine-Cysteine-Transporter (ASCT) 1, the sodium-coupled neutral amino acid transporter (SNAT) 3 and the L Amino Acid Transporter (LAT) 2 in striatum, hippocampus and cortex of male and female mice using Western Blot analysis. Present results demonstrate brain region and transporter-specific changes occurs in female system xc(-) null mice with increased expression of EAAT1 and ASCT1 occurring in the striatum and cortex, respectively, and decreased SNAT 3 expression in cortex. In male system xc(-) null brain, only SNAT3 was altered significantly - increasing in the cortex, but decreasing in the striatum. Total levels of GSH and CyS were similar to that found in age and sex-matched littermate control mice, however, reductions in the ratio of reduced to oxidized GSH (GSH/GSSG) - a hallmark of oxidative stress - were found in all three brain regions in female system xc(-) null mice, whereas this occurred exclusively in the striatum of males. Protein levels of Superoxide dismutase (SOD) 1 were reduced, whereas SOD2 was enhanced in the hippocampus of male xc(-) null mice only. Finally, striatal vulnerability to 3-nitropropionic acid (3-NP)-mediated oxidative stress in either sex showed no genotype difference, although 3-NP was more toxic to female mice of either genotype, as evidenced by an increase in moribundity as compared to males. |
