The expression of many genes is under the control of """"""""regulatory genes"""""""" whose products are required as transcription factors to selectively turn on and off gene expression. This project will evaluate the potential effects of specific enviromental agents on these transcription factors and how such effects may influence changes in target genes and subsequent gene products. The developing nervous system expresses a very high number which are necessary to bring about the successful execution of the developmental program. Any alterations in this process could have a major impact on the developmental cascade of the nervous system. This project has been conducted in vivo in the postnatally developing rat. Development exposure to inorganic lead (lead acetate) alters the expression of mRNA for ornithine decarboxlyase in a brain regionally specific manner. Differential effects are seen depending on the developmental period of lead exposure and the stage of development during exposure. This cellular perturbation may be associated with the altered neural development characteristic of low level lead exposure. Alterations have been seen in the expression of mRNAs for neuronal growth associate proteins as well as specific genes. The pattern of alteration is dependent upon the time of exposure and the specific brain region examined. This project will further examine alterations in mRNAs of specific cellular components of neuronal and glial cells and the interactive signalling during the developmental process. Further examination of these processes will be conducted both in vivo and in vitro (primary cell culture of cerebellar granule cells, astrocytes, and oligodendroglia).
