An acute glutamate exposure induces long-term down regulation of GLAST/EAAT1 uptake activity in cultured bergmann glia cells

Daniel Martínez, Lucía García, José Aguilera, Arturo Ortega

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Glutamate, the major excitatory neurotransmitter in the vertebrate brain, is a potent neurotoxin therefore its extracellular levels have to be tightly regulated by means of sodium-dependent glutamate uptake systems of the slc1A family. The glial glutamate/aspartate transporter (GLAST/EAAT1) and the glutamate transporter 1 carry most of the uptake activity in cerebellum and in the forebrain, respectively. In the cerebellar cortex, GLAST is profusely expressed in Bergmann glia cells, which completely enwrap the parallel fiber-Purkinje cells synapses. Glutamate exposure in these cells, down regulates the activity as well as the expression levels of this transporter. In order to characterize the persistence of a single glutamate exposure, we followed the [3H]-d-aspartate uptake activity as a function of time after the removal of the glutamatergic stimulus. We were able to demonstrate that a single 30 min exposure to glutamate reduces the uptake activity for up to 3 h. This effect is dose-dependent and it is not reproduced neither by ionotropic nor metabotropic glutamate receptors agonists. In contrast, transporter specific ligands such as d-aspartate or l-(-)-threo-3-Hydroxyaspartic acid fully reproduce the glutamate effect. Equilibrium binding experiments revealed a decrease in [3H]-d-aspartate Bmax without a significant change in affinity, clearly suggesting that a reduction in the availability of plasma membrane glutamate transporters is the molecular basis of this effect. Interestingly, neither Glast mRNA nor its protein levels were significantly reduced upon the single glutamate exposure. Taken together, these results favor the notion of a transporter-mediated tight control of the uptake process. © 2013 Springer Science+Business Media New York.
Original languageEnglish
Pages (from-to)142-149
JournalNeurochemical Research
Volume39
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Bergmann glia
  • Glutamate transporters
  • Signaling

Fingerprint Dive into the research topics of 'An acute glutamate exposure induces long-term down regulation of GLAST/EAAT1 uptake activity in cultured bergmann glia cells'. Together they form a unique fingerprint.

Cite this