propylthiouracil and Attention-Deficit-and-Disruptive-Behavior-Disorders

Purpose of this study is to conduct risk assessment of EDCs for the development of CNS in humans by extrapolation from the results of behavioral tests in rats and monkeys. Our hypotheses on the mechanism which gives an adverse effect of EDCs to the developing neural systems are as follows. Thyroid hormone (TH) disrupting chemicals induce deterioration of neural development and estrogen (E2) agonistic chemicals may disturb apoptosis of fetal neural cells resulting in injury of normal neural circuit. The strategy of this study is a bottom up system; for example, basic information was obtained by an experiment using rats and then an experiment using monkey was designed to adapt the results from rats. The monkey experiment data will be assessed in comparison with human behavior. The tactics of this study are, however, a top down system. It is neural behaviors which are an end point evaluation that are primarily performed. They are mother-infant interactions, social behaviors, open field test, memory and learning tests, etc. As for analysis of the mechanism of EDCs' adverse effect, we tried two methods: one is an in vivo drug biased test which interferes with the monoamine oxidase (MAO) system and the other is an in vitro primary neural cell culture. EDCs including BPA, NP, propylthiouracil (PTU) and PCB-OH are injected orally to pregnant rats from gestation day 3 (GD3) to post natal day 21 (PND21) at weaning and their offspring were tested. On the other hand TCDD, BPA and PCB effect are assessed in rhesus monkey or cynomolgus monkey offspring. The study is still continuing and we will present the results obtained to date.

Topics: Animals; Apoptosis; Attention Deficit and Disruptive Behavior Disorders; Behavior, Animal; Benzhydryl Compounds; Endocrine System; Environmental Pollutants; Estrogens, Non-Steroidal; Female; Haplorhini; Humans; Maternal Exposure; Monoamine Oxidase; Nervous System; Phenols; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Pregnancy; Propylthiouracil; Rats