The broad, long-term objective of this research is to provide a comprehensive evaluation of the effects of in utero methylmercury (MeHg) exposure at different stages of the life span of Macaca fascicularis monkeys. Previous studies of Macaca fascicularis exposed in utero to MeHg and controls have described effects during infancy, adolescence and adulthood. The primary goal of the initial 2 years of this application is to continue to assess the effects of in utero MeHg exposure on the adult functioning of these same monkeys using operant procedures that are also sensitive to changes in function typically observed in primates during aging. The primary goal of the last 3 years is to provide housing and care for these monkeys to keep the group together for later studies of MeHg and aging effects on performance.
The specific aims of the studies proposed in years 1 and 2 of this application are to test the following hypotheses: (1) In utero MeHg exposure results in high-frequency hearing impairment in adult Macaca fascicularis. MeHg exposed monkeys will exhibit elevated hearing thresholds at frequencies of 25,000 Hz and above on a test of pure tone detection, (2) In utero MeHg exposure slows the speed of information processing in adult Macaca fascicularis. MeHg exposed monkeys will exhibit increased reaction times compared to controls on a Choice Reaction Time test as the number of response choices increase, and (3) In utero MeHg exposure results in impaired spatial memory in adult Macaca fascicularis. MeHg exposed monkeys will exhibit significant decreases in % correct responses on an Indirect Delayed Response test that uses irrelevant stimuli to interfere with attention and memory. During years 3-5, the specific aims of the project are to: (1) provide housing and care for these monkeys to keep the group together for further studies after this grant period, and (2) evaluate visuospatial orientation, fine and gross motor coordination, menstrual cyclicity, and the general health status of these monkeys using observational techniques in order to detect gross changes related to MeHg exposure and/or aging. Future studies will be aimed at evaluating the effects of in utero MeHg exposure on the performance of these monkeys at a stage in the life span when impaired functions due to aging are typically observed. Exposure of the fetus to MeHg via maternal consumption of contaminated fish continues to be a major public health concern. The major focus of the public health concern regarding MeHg exposure is the possible immediate and long-term effects of in utero exposure on postnatal growth and function. This study was designed to complete our evaluation of the effects of in utero MeHg exposure on adult primate sensory and N cognitive functioning, while providing baseline data for studies of these monkeys after this grant period, when the monkeys are 19 years of age and over. The proposed studies take full advantage of the history of these monkeys and represents the best possible use of this valuable resource.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Toxicology Subcommittee 2 (TOX)
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Kirshner, Annette G
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University of Washington
Public Health & Prev Medicine
Schools of Public Health
United States
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