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

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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.

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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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  1. Department of Neurology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA

    Krishna Banaudha & Ann M. Marini

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  1. Krishna Banaudha
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  2. Ann M. Marini
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Correspondence to Ann M. Marini.

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Banaudha, K., Marini, A.M. AMPA prevents glutamate-induced neurotoxicity and apoptosis in cultured cerebellar granule cell neurons. neurotox res 2, 51–61 (2000). https://doi.org/10.1007/BF03033327

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  • DOI: https://doi.org/10.1007/BF03033327

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