Beta-amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: modulation of uptake as a survival mechanism

Neurobiol Dis. 2004 Apr;15(3):580-9. doi: 10.1016/j.nbd.2003.12.006.


Glutamate transporters are vulnerable to oxidants resulting in reduced uptake function. We have studied the effects of beta-amyloid(25-35) (beta A(25-35)) on [(3)H]-glutamate uptake on cortical neuron or astrocyte cultures in comparison with a scrambled peptide (SCR) and dihydrokainic acid (DHK), a prototypic uptake inhibitor. beta A(25-35) was more potent than DHK in inhibiting glutamate uptake and the effects of both were more marked on astrocytes than on neurons. At 24 h, beta A(25-35) dose-dependently (0.5-15 microM) increased glutamate levels in media from neuron cultures. DHK only enhanced extracellular glutamate at the highest concentration tested (2500 microM). beta A(25-35) induced gradual neurotoxicity (0.1-50 microM) over time. Exposure to beta A(25-35) resulted in increased uptake in astrocytes (0.25-5 microM) and neurons (0.5-15 microM) surviving its toxic effects. However, exposure to DHK (2.5-2500 microM) did not induce neurotoxicity nor modulated uptake. These results indicate that, while inhibition of glutamate uptake may be involved in the neurotoxic effects of beta A(25-35), enhancement of uptake may be a survival mechanism following exposure to beta A(25-35).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Survival
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glutamic Acid / drug effects
  • Glutamic Acid / metabolism*
  • Immunohistochemistry
  • Kainic Acid / analogs & derivatives*
  • Kainic Acid / pharmacology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology
  • Rats


  • Amino Acid Transport System X-AG
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (25-35)
  • Glutamic Acid
  • dihydrokainic acid
  • Kainic Acid