Friday, February 26, 2016
Room 130 Pharmacy Building
Developmental Pyrethroid Exposure Reproduces Features of Attention-Deficit Hyperactivity Disorder:
Role of Epigenetic Alterations in the Dopamine System
Jason R. Richardson, MS, PhD, DABT
Pharmaceutical Sciences and Neurodegenerative Disease Research Focus Area
Northeast Ohio Medical University
Summary: Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-aged children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Using behavioral, molecular, and neurochemical techniques we determined that mice exposed to the pyrethroid pesticide deltamethrin during development reproduce features of ADHD. Features include elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased D1 dopamine receptor levels and the DAT appear to be responsible for the behavioral deficits and are driven by epigenetic changes in DNA methylation and histone acetylation, respectively. Epidemiological data reveal that children aged 6-15 with detectable levels of pyrethroid metabolites in their urine were more than twice as likely to be diagnosed with ADHD and that boys are more affected than girls. Our epidemiological finding, combined with the recapitulation of ADHD behavior in pesticide treated mice, provides a mechanistic basis to suggest that developmental pyrethroid exposure is a risk factor for ADHD.
Biography: Jason Richardson PhD DABT is a tenured Professor in the Department of Pharmaceutical Sciences at Northeast Ohio Medical University, board-certified toxicologist and the Founding Director of a University-wide Research Focus Area in Neurodegenerative Disease and Aging. He received his Bachelor’s degree from Northeast Louisiana University (now University of Louisiana at Monroe) where he majored in Toxicology. He received his M.S. and Ph.D. degrees from Mississippi State University and then completed postdoctoral training at Emory University, where he was jointly appointed at the Rollins School of Public Health and the Center for Neurodegenerative Disease in the School of Medicine. Dr. Richardson spent 10 years at Rutgers University as a faculty member at Robert Wood Johnson Medical School and the Environmental and Occupational Health Sciences Institute where he served as Deputy Director and then Director of the Joint Graduate Program in Toxicology at Rutgers University. Dr. Richardson has authored or co-authored over 70 manuscripts and book chapters in the areas of developmental neurotoxicology, neurodegenerative disease, and pesticides. He is an Associate Editor for Neurotoxicology and was an Associate Editor for BMC Neurology. He has served as a reviewer and Chair for several NIH panels, the Michael J. Fox Foundation for Parkinson’s Disease Research, Health Canada, and the United Kingdom Parkinson’s Disease Society. He has served as PI on grants with direct costs totaling ~$6.5 million. He is currently PI on NIH grants that aim to determine the role of genetic susceptibility to neurotoxicity in Parkinson’s disease, identifying novel targets for reducing neuroinflammation in Parkinson’s disease and to develop drugs to mitigate acute neurotoxicant exposures as part of the HHS Counterterrorism Initiative (CounterAct).