This proposal is a supplementary request to NIEHS grant ES01503, which is in its second year of funding. The original application proposes to examine the neurotoxic effects of low-level lead exposure during early postnatal development in rats. The research emphasizes functional analysis of the hippocampus, a neural system known to be affected by lead poisoning. The hippocampus is rich in lead and zinc and is thought to be important in plumbism's neurological sequelae. Functional assays include electrophysiology of the developing hippocampus, neuropharmacological responsiveness of hippocampal neurotransmitter systems, and behavioral measures related to the hippocampus. Neurohistological studies by light microscopy were proposed to examine the effect of lead on hippocampal morphological development. Seizure responsiveness is examined by the maximal electroshock seizure and electroshock seizure threshold tests. The hypothesis that one mechanism of lead neurotoxicity may be displacement of zinc by lead at neural sites is to be tested by determination of lead and zinc concentrations in the hippocampus and several other brain regions. An attempt will be made to modify the neurotoxic consequences of lead exposure by manipulation of dietary zinc intake. The intent of this supplementary proposal is to obtain monies to expand our research program and facilities. An additional electrophysiology project, kindling of the hippocampus, is proposed and additional equipment is requested to increase the capabilities and reliability of our currently limited and outdated electrophysiology laboratory. The neurohistological measurement has been modified from light microscopic study of the whole hippocampus to electron microscopic (EM) study of mossy fiber synaptogenesis. Preliminary studies have shown that the EM investigation is more fruitful than the light histological study proposed initially. Funds are requested for the increased supply costs of EM histology and to support a graduate student EM technician. An additional measure of seizure responsiveness -- spinal cord convulsions -- is proposed and an appropriate electrical stimulation unit is requested.
NIH ExPorter
NIH ExPorter