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Neurotoxicity Research

, Volume 2, Issue 1, pp 51–61 | Cite as

AMPA prevents glutamate-induced neurotoxicity and apoptosis in cultured cerebellar granule cell neurons

  • Krishna Banaudha
  • Ann M. MariniEmail author
Article

Abstract

Exposure of cultured cerebellar neurons to ±-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the presence of aniracetam protects all of the vulnerable neurons against the excitotoxic actions of glutamate acting on N-methyl-D-aspartate receptors. The protective effect of AMPA was both time- and concentration-dependent. Aniracetam alone did not protect the neurons against the excitotoxic effects of glutamate. Pretreatment of cerebellar neurons with the AMPA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione blocked the neuroprotective effect mediated by AMPA indicating that the neuroprotective effect is mediated specifically by AMPA receptors. An excitotoxic concentration of glutamate, which killed between 60–80% of granule cell neurons on day 8in vitro, mediated its toxic effect via a time-dependent apoptotic pathway. Pretreatment of cerebellar granule cell neurons with AMPA (500 μM) completely blocked glutamate-mediated apoptosis. Our results suggest that AMPA receptors may play an important role in neuronal survival.

Keywords

AMPA Glutamate Excitotoxicity Cerebellar neurons Apoptosis Neuroprotection 

Abbreviations

AMPA

μ-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid

CNQX

6-cyano-7-nitroquinoxaline-2,3-dione

Ani

aniracetam

NMDA

N-methyl-D-aspartate

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Copyright information

© Springer 2000

Authors and Affiliations

  1. 1.Department of NeurologyUniformed Services University of the Health SciencesBethesdaUSA

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