Glutamate Transporter Expression and Function in Human Glial Progenitors

Nicholas J. Maragakis, Joerg Dietrich, Victor Wong, Haipeng Xue, Margot Mayer-Proschel, Mahendra S. Rao, Jeffrey D. Rothstein

Research output: Contribution to journalArticlepeer-review

Abstract

Glutamate is the major neurotransmitter of the brain, whose extracellular levels are tightly controlled by glutamate transporters. Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes. EAAT1, EAAT3, and EAAT4 are all expressed in GRPs with a subsequent upregulation of EAAT1 following differentiation of GRPs into GRP-derived astrocytes in the presence of bone morphogenic protein (BMP-4). This corresponds to a significant increase in the glutamate transport capacity of these cells. EAAT2, the transporter responsible for the bulk of glutamate transport in the adult brain, is not expressed as a full-length protein, nor does it appear to have functional significance (as determined by the EAAT2 inhibitor dihydrokainate) in these precursors. A splice variant of EAAT2, termed EAAT2b, does appear to be present in low levels, however. EAAT3 and EAAT4 expression is reduced as glial maturation progresses both in astrocyte precursors and early-differentiated astrocytes and is consistent with their role in adult tissues as primarily neuronal glutamate transporters. These human glial precursors offer several advantages as tools for understanding glial biology because they can be passaged extensively in the presence of mitogens, afford the potential to study the temporal changes in glutamate transporter expression in a tightly controlled fashion, and are cultured in the absence of neuronal coculture, allowing for the independent study of astroglial biology.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalGlia
Volume45
Issue number2
DOIs
StatePublished - Jan 15 2004

Keywords

  • Astrocyte
  • Development
  • Human
  • Transporter

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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