One purpose of membrane-related studies has been to delineate injury to discrete neuronal tracts. This has the goal of identification of damage to specific circuitry which is especially vulnerable to a given neurotoxic agent. This project has involved study of the effect of various neurotoxic agents upon neurotransmitter translocations in the synaptic region. High-affinity uptake systems, calcium stimulated neurotransmitter release and assay of receptor binding sites have been carried out in animals treated with organometals. The differential susceptibility of various brain regions to trimethyltin and triethyl tin has been studied in this manner and data related to morphological findings. In the case of triethyl lead studies, biochemical behavioral correlations between analgesia and benzodiazepine binding sites have been made. A second goal is to study less selective damage to cerebral membranes. Such general effects may still present as specifically damaging certain nerve pathways, perhaps because of their intrinsic sensitivity to insult. This work focuses on the effect of agents upon levels of free calcium within the synaptosome and on depolarization-induced calcium fluxes across the synaptosomal membrane. Novel methods of assaying these parameters have been adapted for our studies. This work will also involve determination of membrane fluidity by use of fluorescent probes.
