Transporter-mediated L-glutamate elimination from cerebrospinal fluid: Possible involvement of excitatory amino acid transporters expressed in ependymal cells and choroid plexus epithelial cells

Shin ichi Akanuma, Tatsuhiko Sakurai, Masanori Tachikawa, Yoshiyuki Kubo, Ken ichi Hosoya

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Background: L-Glutamate (L-Glu) is the major excitatory neurotransmitter in the CNS, and its level in cerebrospinal fluid (CSF) is reported to be increased in neuroexcitatory diseases such as epilepsy. Since L-Glu concentration in the CSF is reported to be lower than that in plasma, it has been proposed that some mechanisms of L-Glu clearance from the CSF operate in the brain. The purpose of this study was to elucidate the major pathway of L-Glu elimination from rat CSF and the transporters responsible. Methods: Protein expression and localization of excitatory amino acid transporters were examined by immunohistochemical analysis using specific antibodies. In vivo elimination of L-Glu from rat CSF was evaluated by intracerebroventricular administration. An L-Glu uptake study by using primary-cultured rat ependymal cells and isolated rat choroid plexus was performed to characterize L-Glu transport mechanisms. Results: An immunohistochemical analysis has shown that excitatory amino acid transporter (EAAT) 1 and EAAT3, which are D-aspartate-sensitive and kainate-insensitive L-Glu transporters, are localized on the CSF-side of rat ependymal cells and choroid plexus epithelial cells, respectively. In contrast, the kainate-sensitive L-Glu transporter, EAAT2, is not expressed in these cells. In vivo L-Glu elimination clearance from the rat CSF (189 μL/(min · rat)) was 23-fold higher than the CSF bulk flow rate, indicating that facilitative process(es) are involved in L-Glu elimination from the CSF. The in vivo [3H]L-Glu elimination from the CSF was significantly inhibited by unlabeled L-Glu and D-aspartate, but not kainate. Moreover, unlabeled L-Glu and D-aspartate inhibited [3H]L-Glu uptake by rat ependymal cells and choroid plexus epithelial cells, whereas kainate had little effect. Conclusion: It is suggested that EAAT1 in ependymal cells and EAAT3 in choroid plexus epithelial cells participate in L-Glu elimination from the CSF.

Original languageEnglish
Article number11
JournalFluids and Barriers of the CNS
Volume12
Issue number1
DOIs
Publication statusPublished - 2015 Apr 29

Keywords

  • Blood-cerebrospinal fluid barrier
  • Cerebrospinal fluid
  • EAAT1
  • EAAT3
  • Ependymal cells
  • Excitatory amino acid transporter
  • Glutamine synthase
  • L-glutamate

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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