For several years the applicant has been studying the neurotoxic properties of the putative excitatory transmitters, glutamate and asparate and certain structural analogs -- the so-called excitotoxic amino acids. Recently he observed that other excitatory agents found naturally in brain such as folic acid and acetylcholine, mimic neurotoxic properties of the powerful excitotoxic glutamate analog, kainic acid. The applicant proposes to study mechanisms by which endogenous neuroexcitants destroy central neurons and to explore possible roles of excitatory mechanisms in human neuropathological conditions such as epilepsy-related brain damage, lithium neurotoxicity, tardive dyskinesia and neuronal degeneration associated with aging. A combined ultrastructural, immunohistochemical, neurochemical, neuropharmacological, behavioral and chemical lesioning approach will be employed.
