Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Thyroid hormone (TH) is an important regulator of brain development and TH insufficiency causes neurodevelopmental deficits. Ammonium perchlorate (AP), used as an oxidizing agent in the manufacture of solid rocket fuel, explosives, etc., inhibits the uptake of iodine, which is essential for TH synthesis, and decreases TH release. Since perchlorate accumulates in breast milk, its environmental contamination may expose infants to high concentrations. The present study investigated the maternal exposure effect of AP on offspring hippocampal neurogenesis as a highly sensitive endpoint of developmental neurotoxicity. Maternal rats were administered AP in drinking water at doses of 0, 300, and 1,000 ppm from gestation day 6 to day 21 post-delivery at weaning, according to the OECD Test Guideline 426. At the end of exposure, both dams and offspring showed thyroid follicular cell hyperplasia at 300 ppm and 1000 ppm, and offspring showed decreased serum T3 and T4 levels at 1,000 ppm. In the neurogenic niche, AP decreased the numbers of type-1 neural stem cells and type-2a and type-2b neural progenitor cells by suppressing their proliferation, suppressed ARC-dependent synaptic plasticity, and decreased the number of PVALB+ interneurons at the end of exposure, similar to the previously reported changes for antithyroid drugs. In contrast, RELN+ interneurons were inconsistently decreased in number, suggesting an inhibition of stem cell quiescence or maintenance. At the adult age on postnatal day 77, all the changes were disappeared, suggesting a transient fashion of disruptive neurogenesis.