Director: Merle G. Paule, Ph.D.

Brain disorders and other nervous system-related disorders account for more hospitalizations than any other major disease group in the U.S. with approximately one in four Americans suffering a brain-related disorder sometime during their lives. Recent advances in biomedical research are currently providing scientists with a variety of new tools with which to better understand the etiology of brain-related disorders and to further reduce the risks associated with exposure to neuroactive substances. It has long been known or suspected that the causes of brain-related disorders include exposure to chemicals such as therapeutic drugs, food additives, food stuffs, cosmetic ingredients, pesticides, and naturally occurring substances. Since the number of potential neurotoxicants that require FDA regulation is estimated to be in the thousands, it is critical that methods be developed to assess neurotoxic risk. It is clear that chemicals from the categories listed above are vital to the national economy and our quality of life; therefore, the challenge is to determine at what dose and under what conditions these compounds can be used while minimizing the likelihood that they will cause adverse effects on the nervous system. In addition, it will be important to determine individual characteristics, such as genetic or metabolic, that affect a person's response to neurotoxic insult.

The overall goals of the Division are to develop and validate quantitative biomarkers and identify biological pathways associated with the expression of neurotoxicity. An increased understanding of processes associated with neurotoxic outcomes will provide opportunities for improved assessments of risk and identification of potential therapeutic approaches. The strategy for achieving these goals is to employ multidisciplinary approaches that capitalize upon the Division's expertise in neurochemistry, molecular neurobiology, neuropathology, neurophysiology, and behavior. Some of the more unique features of our research capabilities include the ability to:

1. determine chemical concentrations and cellular-level interactions in target tissue
2. determine changes in gene and protein expression associated with chemical exposures
3. employ multiple species, including nonhuman primates, rodents, and occasionally humans, in the risk-assessment process to reduce the uncertainty associated with extrapolating findings across species.

The NCTR Research Plans and Accomplishments Document contains information on the latest accomplishments and plans for the Division of Neurotoxicology as well as project and publication listings.