You are here:
ONTOGENY OF PROTEINS FOR USE AS BIOMARKERS OF DEVELOPMENTAL NEUROTOXICITY.
Citation:
Robinette, B. L. AND W R. Mundy. ONTOGENY OF PROTEINS FOR USE AS BIOMARKERS OF DEVELOPMENTAL NEUROTOXICITY. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
The developing nervous system can be uniquely susceptible to adverse effects following exposure to environmental chemicals, and several advisory panels (e.g. ILSI, NRC, NAS) have highlighted the need for rapid and sensitive developmental neurotoxicity testing methods. Measurement of changes in biochemical markers that are linked to the cellular processes underlying nervous system development is one approach to developing such methods. The current research examined the ontogeny of proteins in the CNS that are associated with neuronal differentiation and growth. Frontal cortex and hippocampal tissue were obtained from male Long Evans rats on postnatal days 1, 7, 14, 21, 28, and 83-125 (adults) and the expression of structural and signaling proteins was determined by SDS-PAGE and western blotting optimized with respect to antibody dilution and protein load to obtain semi-quantitative results. The expression of GAP-43 and tau, proteins associated with axonal and dendritic elongation, was high during the early postnatal period and decreased by one half in adulthood. In contrast, expression of the synaptic proteins synapsin and synuclein increased 15-fold from very low levels on postnatal day 1 to maximal levels at adulthood. SMAD, CREB, ERK, and CaMKII are all signaling proteins that are part of pathways activated during neuronal growth and synaptic plasticity. Expression of all four proteins increased during development (SMAD 2-fold; CREB 10-fold; ERK 3-fold, CaMKII 100-fold). However, the levels of the phosphorylated (active) form of these proteins were highest during the early postnatal period then decreased during adulthood. The unique ontogeny of these proteins suggests that they can be used to monitor several aspects of nervous system development. Further research will determine whether changes in the ontogenic profile of these proteins can be used to detect developmental neurotoxicity produced by environmental chemicals. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).