During the development of the nervous system, the temporal and spatial regulation of gene expression is a critical component of neural and glial growth, development, and interactions. These critically timed events are assumed to be a major component in the differential susceptibility of the developing organism to environmental insult. This project examined chemical induced perturbations during development of the NS as indicated by alterations in the spatio-temporal expression of mRNA for various developmentally regulated proteins associated with distinct processes of development. We have shown by RNase protection assays that lead acetate alters developmentally regulated structural proteins for neurons and glia in the rat as well as an upregulation of apoptosis genes and brain derived neurotrophic factors. Early exposure to mercury vapors also elevate mRNA levels for apoptosis factors consistent with previous reports of mercury induced apoptosis in the brain. This technique is being expanded with the establishment of new probe sets to detect mRNA levels for proteins associated with the various cell types and stages of brain development. Future Research: The developmental related effects of chemicals which disrupt thyroid hormone levels, PTU and dioxin, will be examined to determine any relationship with structural alterations in the nervous system. Additional studies are based upon events associated with hypoxia- ischemia occurring at preterm birth. These studies will examine the acute toxicity of interleukin 6 on the early post-natal developing CNS and alteration in the normal ontogeny of molecular markers for cortical neuronal network development. - mouse, rat, brain, development, lead acetate, mercury vapors, hypoxia
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