The toxic effects of glutamate and related compounds in the retina and the brain

Abstract

This paper has reviewed information pertaining to an interesting group of amino acids--glutamate, aspartate, and certain of their structural analogs, some of which are neurotransmitter candidates, and all of which have both neuroexcitatory and neurotoxic activities. Evidence for the excitotoxic concept, which holds that an excitatory and possibly synapse-related mechanism underlies the neurotoxicity of these compounds, is presented. Unlike a number of environmental neurotoxicants which induce toxic changes primarily in axons, these agents attack the dendrosomal portions of the neuron, which has led to their use as "axon-sparing" lesioning agents. When administered either systemically or by direct microinjection into the CNS, they delete intrinsic neurons from infiltrated regions without disturbing axons that are passing through or terminating therein. They are potentially useful tools, therefore, for studying anatomical pathways and structure-function relations in the CNS. The basis for their use as systemic investigational tools--that they have access from blood to the retina and specialized regions of brain, the circumventricular organs--is also the basis for considering them potentially hazardous for use as food additives or drugs. Ways in which the consumer may be exposed to these agents are considered and relevant mechanisms of risk are discussed.