Student Research: Nicole M. DeFrank
, Environmental Toxicology (Tox), 2004
Faculty Advisor: Elaine M. Faustman
Computing Model of Radiation-Induced Abnormalities of the Neocortex
Substantial evidence has demonstrated that low dose radiation exposures (10 to 50 cGy) during particular gestational periods can result in permanent neuronal perturbations and eventual abnormalities in behavior and mental activity. It is hypothesized that the mechanisms underlying these effects include radiation-induced cell death among neuronal precursors and perturbed migration patterns of post-mitotics neurons. These effects disrupt the normal processes and timing of neurogenesis and lead to insufficient neuron production and/or improper positioning of neurons. Existing data sets were used in the construction of a computational model to describe the extent of cell death and altered patterns of neuronal migration in the mouse neocortex after radiation exposure in utero. The subsequent effects on neuron number and differentiation status at the end of neurogenesis were determined and related to the probability of decreased learning ability. Model results indicate that radiation-induced damage among neuronal precursors leads to variable rates of cell death in a dose and time dependent manner, with the most drastic effects corresponding to times of rapid proliferation and differentiation. Surviving cells exhibit slowed replication rates and the migration of post-mitotic neuronal cells altered, leading to the improper placement mature neurons. This model is of utility for risk assessment as it includes the evaluation of alterations in specific developmental dynamic processes, incorporates in vitro data, and permits comparisons of toxicant effects across various times and doses.
Taken from the beginning of thesis.