Effect of Lead, Manganese and Stress During Development

Cincinnati Childrens Hosp Med Ctr, Cincinnati OH

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Abstract

Learning and behavior problems among US children appear to be rising steadily, however the etiology for[unreadable] these behavioral changes is unknown. Exposure to low-levels of various neurotoxins has been suggested[unreadable] as a potential factor in these changes. For example, low levels of lead are known to be associated with[unreadable] learning deficits and social behavior problems. One issue with animal models for the effects of various[unreadable] neurotoxins is that they are limited to investigating only one factor even though human exposures occur[unreadable] together with many other environmental factors. For example, it is known that there is a differential exposure[unreadable] to heavy metals in low social economic status households. Therefore, we will investigate the effects of lead[unreadable] and manganese (since manganese is known to potentiate the increase in the amount of lead that[unreadable] accumulates in the brain) in combination with stressors (isolation, overcrowding, or limited resources with[unreadable] maternal depression) to mimic human conditions. The first aim is to determine which stressor has the[unreadable] greatest impact on heavy metal exposure by measuring physiological parameters during the period of[unreadable] administration as well as investigating the long-term effects of this combination on neurotransmitters and[unreadable] long-term potenitation induction. The second aim is to investigate the dose-dependency of lead or[unreadable] manganese in combination with stress on the learning ability and social aspects of the animals. We will be[unreadable] using a novel approach to investigating learning and memory in these animals by using a combination of[unreadable] learning tests that test different types of learning. This is relevant to how humans would have to learn as[unreadable] well. This aim will provide a foundation to model low level exposure and to understand the functional[unreadable] changes that occur. The third aim is to combine lead, manganese and stress and assess the impact of this[unreadable] more relevant combination to human exposures on learning and memory and social behavior. The last aim[unreadable] is designed to investigate the developmental changes that occur related to the three combination exposure[unreadable] by using MRI as well as looking at the nuerophysiological response when the animals are adults. These[unreadable] studies will provide much needed data on the low-level effects of neurotoxins in combination with[unreadable] environmentally relevant stressors. Potential mechanisms will be explored by investigating neurotransmitter[unreadable] and neuroendocrine systems and the glutamate receptor complex.