Immunohistochemistry of aberrant neuronal development induced by 6-propyl-2-thiouracil in rats

6-Propyl-2-thiouracil (PTU)-induced hypothyroidism disrupts neuronal/glial development. This study sought to identify the sensitive immunohistochemical parameters of developmental neurotoxicity (DNT) following PTU-exposure, as well as their responses in a 28-day toxicity study in adults. In the developmental exposure study, pregnant rats were treated with 0, 1, 3, and 10ppm PTU in drinking water from gestational day 6 to postnatal day (PND) 21 and pups were examined on PNDs 21 and 77. In the adult-stage exposure study, 5-week-old male rats were treated with 0, 0.1 and 10mg PTU/kg by oral gavage for 28 days. In the developmental exposure study on PND 21, there were fewer GFAP⁺, PAX6⁺, and DCX⁺ cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus at ≥3 or 10ppm. Regarding synaptic plasticity-related molecules, there were fewer EPHA4⁺ and ARC⁺ cells in the dentate granule cell layer. Regarding GABAergic interneuron subpopulations, there were more RELN⁺, CALB2⁺, and SST⁺ cells and fewer PVALB⁺ cells in the dentate hilus. There were also differences in the numbers of RELN⁺, PVALB⁺, CALB2⁺, and NPY⁺ cells in the cerebral cortex, and RELN⁺, PVALB⁺, and SST⁺ cells in the cerebellar cortex. Most of these changes were sustained until PND 77. Following adult-stage exposure (10mg/kg), there were fewer SGZ DCX⁺ cells, but more RELN⁺ and SST⁺ cells in the dentate hilus. Results suggest that GABAergic interneuron populations in cortical tissues, hippocampal neurogenesis, and synaptic plasticity are sensitive to PTU-induced DNT during development. In contrast, only hippocampal neurogenesis was sensitive to adult-stage exposure.