Glycine-induced neurotoxicity in organotypic hippocampal slice cultures

Abstract

The role of the neutral amino acid glycine in excitotoxic neuronal injury is unclear. Glycine coactivates glutamate N-methyl-D-aspartate (NMDA) receptors by binding to a distinct recognition site on the NR1 subunit. Purely excitatory glycine receptors composed of NR1 and NR3/NR4 NMDA receptor subunits have recently been described, raising the possibility of excitotoxic effects mediated by glycine alone. We have previously shown that exposure to high concentrations of glycine causes extensive neurotoxicity in organotypic hippocampal slice cultures by activation of NMDA receptors. In the present study, we investigated further properties of in vitro glycine-mediated toxicity. Agonists of the glycine recognition site of NMDA receptors (D-serine and D-alanine) did not have any toxic effect in hippocampal cultures, whereas competitive blockade of the glycine site by 7-chlorokynurenic acid was neuroprotective. Stimulation (taurine, β-alanine) or inhibition (strychnine) of the inhibitory strychnine-sensitive glycine receptors did not produce any neurotoxicity. The toxic effects of high-dose glycine were comparable in extent to those produced by the excitatory amino acid glutamate in our model. When combined with sublethal hypoxia/hypoglycemia, the threshold of glycine toxicity was decreased to less than 1 mM, which corresponds to the range of concentrations of excitatory amino acids measured during in vivo cerebral ischemia. Taken together, these results further support the assumption of an active role of glycine in excitotoxic neuronal injury.

DOI: 10.1007/s00221-004-2079-7

5 Figures and Tables

Statistics

0100200300200920102011201220132014201520162017
Citations per Year

257 Citations

Semantic Scholar estimates that this publication has 257 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Barth2004GlycineinducedNI, title={Glycine-induced neurotoxicity in organotypic hippocampal slice cultures}, author={Aaron C M Barth and Lieu B. Nguyen and Lydia Barth and David Newell}, journal={Experimental Brain Research}, year={2004}, volume={161}, pages={351-357} }