Chapter 26 - Glutamate Receptor-Mediated Neurotoxicity

Abstract

This chapter provides an overview of the glutamate (glu) receptor-mediated neurotoxicity. Glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS), has vitally important beneficial functions. However, it also harbors treacherous neurotoxic potential. Glu neurotoxicity can be expressed in several different ways, depending on which excitatory amino acid (EAA) receptor subtype is involved and whether the receptor is excessively activated or inhibited. Classical excitotoxicity, the most extensively studied type of neurotoxicity caused by Glu or related EAA, results from excessive activation of EAA ionotropic receptors. Another entirely different form of neurotoxicity is seen following excessive inhibition of a specific subtype of EAA ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor. This chapter reviews the studies that suggest that either excessive activation or suppression of either ionotropic or metabotropic EAA receptors can have neurotoxic consequences and that a variety of different mechanisms may be involved. The distinctive features of each type of mechanism must be taken into consideration in devising protocols for toxicological evaluation of environmental agents suspected of interacting with EAA receptor systems.