Lysophosphatidic acid decreases glutamate and glucose uptake by astrocytes

Jeffrey N. Keller, Marion R. Steiner, Mark P. Mattson, Sheldon M. Steiner

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


The brain is a rich source of the lipid biomediator lysophosphatidic acid, and lysophosphatidic acid levels can significantly increase following brain trauma. Responses of primary rat brain astrocytes to this novel lipid are defined in the current study. Treatment of cells with lysophosphatidic acid resulted in a time- and dose-dependent inhibition of glutamate uptake. Inhibition of glutamate uptake was specific because the related phospholipids, phosphatidic acid, lysophosphatidylcholine, and lysophosphatidylglycerol, did not inhibit this uptake under comparable conditions, i.e., treatment with 10 μM lipid for 30 min. Lysophosphatidic acid treatment of cells resulted in an increase in lipid peroxidation, as measured by the thiobarbituric acid assay. This increase in content of thiobarbituric acid-reactive substances was largely inhibited by treatment with dithiothreitol or propyl gallate; however, such treatment did not affect the lysophosphatidic acid-induced inhibition of glutamate uptake. Lysophosphatidic acid also inhibited glucose uptake with a dose-response curve that paralleled the inhibition of glutamate uptake. By impairing uptake of glutamate by astrocytes, lysophosphatidic acid may exacerbate excitotoxic processes in various neurodegenerative conditions.

Original languageEnglish (US)
Pages (from-to)2300-2305
Number of pages6
JournalJournal of Neurochemistry
Issue number6
StatePublished - Dec 1996
Externally publishedYes


  • Astrocytes
  • Glucose uptake
  • Glutamate uptake
  • Lysophosphatidic acid
  • Thiobarbituric acid-reactive substances

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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