Children living near Superfund sites may be exposed to ground water contaminated with neurotoxicants, which may pose a special health risk because the brain is thought to be particularly vulnerable during childhood. Low-level toxicant exposures may cause subtle and difficult to detect neurological defects that lead to learning disabilities or attention deficit disorders. The goal of this project is to develop animal models that can detect such deficits following exposure to the low concentrations of toxins typically found in ground water near Superfund sites.

Based on well-characterized experiments that demonstrate the role of complex spatial and social experience in brain growth in rats, we have developed a screen to test for faults in brain growth caused by neurotoxicant exposure during development. The general brain growth response correlates well with cognitive ability. Progress has been made on two major objectives: to study the effects of chloroacetaldehyde (CAA-a metabolite of the Superfund chemical vinyl chloride) on brain growth, and to refine our ability to detect specific cellular deficits using methylazoxymethanol (MAM). We have integrated our studies in a collaboration with Drs. Karla Thrall and Glen Kisby, who analyzed CAA metabolism (Thrall) and CAA-induced DNA damage in a variety of tissues (Kisby). We found that CAA retention in the brain is prolonged relative to its presence in peripheral tissues. Studies measuring the effects of CAA exposure on brain development and DNA damage in liver, brain and kidney are ongoing. Our goal is that the protocol we establish for assessing CAA effects in the brain and other tissues can be applied in the future to assess the effects of a wide variety of compounds.

We have also made progress toward refining our model to detect the adverse effects of MAM. We are examining gene expression associated with brain plasticity to determine if this measure will reveal signs of damage more rapidly than measures of brain structure. We have also completed both light and electron microscopic quantitative analyses of the structure of neurons to determine if developmental exposure has a lasting effect on synapses in brain regions important to cognition, learning and memory. In rats dosed prenatally with MAM, we have found that brain development is diminished at dosages significantly lower than those reported previously using conventional assessments of brain structure or behavior.

This study is important because it 1) demonstrates latent developmental damage after low level exposure to an established neurotoxicant (MAM) and 2) provides a new set of biomarkers for assessing low dose effects of as yet uncharacterized compounds to which developing humans are exposed. Our collaboration with other SBRP scientists is significant because it 1) combines the expertise of multiple labs to obtain a new battery of assessments; 2) maximizes the data yield of an experiment; and 3) establishes an integrative training environment for young scientists.