Excitatory Amino Acid Neurotoxicity in Rat Brain Slices
The evidence continues to mount that excessive or prolonged activation of excitatory amino acid (EAA) receptors in the central nervous system contributes to the death of neurones taking place in certain neuropathological conditions of the types that affect humans (Olney 1978; Meldrum and Garthwaite 1990). These conditions include cerebral ischaemia, hypoglycaemia and trauma in which an endogenous agonist, presumably glutamate, is believed to be the culprit. However, following the discoveries that ingestion of the glutamate receptor agonists, domoic acid (in mussels), β-N-oxalylamino-L-alanine (BOAA, in chick peas) and β-N-methyl-amino-L-alanine (BMAA, in the seeds of a false sago palm, Cycas) induces neurodegeneration, attention is also being directed towards glutamate-like chemicals in the environment as neurotoxic agents.
KeywordsPermeability Hydrolysis Toxicity Ischemia NMDA
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- Crepel F, Dhanjal SS, Sears TA (1982) Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study. J Physiol (Lond.) 329:297–317.Google Scholar
- Foster GA, Roberts PJ, Rowlands GJ, Sharif NA (1981) Ontogeny of neurochemical markers for glutamatergic neurons in cerebellum: implications for development of kainate neurotoxicity. Br. J. Pharmacol. 73:235P.Google Scholar
- Garthwaite G, Williams GD, Garthwaite J (1990) AMPA mimics quisqualate neurotoxicity in slices of young rat cerebellum and hippocampus. Neurosci. Lett. Suppl. 38:S78.Google Scholar
- Garthwaite J (1989) NMDA receptors, neuronal development and neuronal degeneration. In: Watkins JC, Collingridge GL (eds.) The NMDA receptor. Oxford University Press, pp 187-205.Google Scholar
- Iino M, Ozawa S, Tsuzuki K (1990) Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J. Physiol. (Lond.) 424:151–165.Google Scholar
- Nielsen EO, Drejer J, Cha J-HJ, Young AB, Honore T (1990) Autoradiographic characterization and localization of quisqualate binding sites in rat brain using the antagonist [3H]6-cyano-7-nitroquinoxaline-2,3-dione: comparison with (R,S)-[3H]a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites. J. Neurochem. 54:686–695.PubMedCrossRefGoogle Scholar
- Olney JW (1978) Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 95–121.Google Scholar