DOI

  • Sigrid Ottestad-Hansen
  • Qiu Xiang Hu
  • Virgine Veronique Follin-Arbelet
  • Eduard Bentea
  • Hideyo Sato
  • Ann Massie
  • Yun Zhou
  • Niels Christian Danbolt

The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes. The labeling specificity was validated using tissue from xCT knockout mice as controls. Astrocytes were selectively labeled, but showed greatly varying labeling intensities. This astroglial heterogeneity resulted in an astrocyte domain-like labeling pattern. Strong xCT labeling was also found in the leptomeninges, along some blood vessels, in selected circumventricular organs and in a subpopulation of tanycytes residing the lateral walls of the ventral third ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive microglia induced by glutamine synthetase deficiency, were unlabeled. The concentration of xCT protein in hippocampus was compared with that of the EAAT3 glutamate transporter by immunoblotting using a chimeric xCT-EAAT3 protein to normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an xCT/EAAT3 ratio close to one (0.75 ± 0.07; average ± SEM; n = 4) in adult C57BL6 mice.

CONCLUSIONS: xCT is present in select blood/brain/CSF interface areas and in an astrocyte subpopulation, in sufficient quantities to support the notion that system xc- provides physiologically relevant transport activity.

Original languageEnglish
Pages (from-to)951-970
Number of pages20
JournalGlia
Volume66
Issue number5
DOIs
Publication statusPublished - May 2018

    Research areas

  • astrocyte heterogeneity, glia, glutamate transporter, system xc−, tanycytes, Immunohistochemistry, Mice, Inbred C57BL, Microfilament Proteins/metabolism, Male, Amino Acid Transport System y+/genetics, Blotting, Western, Mice, Knockout, Animals, Calcium-Binding Proteins/metabolism, Brain/cytology, Astrocytes/cytology, Excitatory Amino Acid Transporter 2/metabolism, Excitatory Amino Acid Transporter 3/metabolism, Female

ID: 36070274