Suppression of Hippocampal Neurogenesis and Oligodendrocyte Maturation Similar to Developmental Hypothyroidism by Maternal Exposure of Rats to Ammonium Perchlorate, a Gunpowder Raw Material and Known Environmental Contaminant.

The environmental contaminant perchlorate raises concern for hypothyroidism-related brain disorders in children. This study investigated the effects of developmental perchlorate exposure on hippocampal neurogenesis and oligodendrocyte (OL) development. Pregnant Sprague-Dawley rats were administered with ammonium perchlorate (AP) in drinking water at concentrations of 0 (control), 300, and 1000 ppm from gestation day 6 until weaning [postnatal day (PND) 21]. On PND 21, offspring displayed decreased serum triiodothyronine and thyroxine concentrations at 1000 ppm and thyroid follicular epithelial cell hyperplasia at ≥300 ppm (accompanying increased proliferation activity at 1000 ppm). Hippocampal neurogenesis indicated suppressed proliferation of neurogenic cells at ≥300 ppm, causing decreases in type-1 neural stem cells (NSCs) and type-2a neural progenitor cells. In addition, an increase of SST+ GABAergic interneurons and decreasing trend for ARC+ granule cells were observed at 1000 ppm. CNPase+ mature OLs were decreased in number in the dentate gyrus hilus at ≥300 ppm. At PND 77, thyroid changes had disappeared; however, the decrease of type-1 NSCs and increase of SST+ interneurons persisted, CCK+ interneurons were increased, and white matter tissue area was decreased at 1000 ppm. Obtained results suggest an induction of hypothyroidism causing suppressed hippocampal neurogenesis (targeting early neurogenic processes and decreased synaptic plasticity of granule cells involving ameliorative interneuron responses) and suppressed OL maturation during the weaning period. In adulthood, suppression of neurogenesis continued, and white matter hypoplasia was evident. Observed brain changes were similar to those caused by developmental hypothyroidism, suggesting that AP-induced developmental neurotoxicity was due to hypothyroidism.

Increased GS-II lectin binding and SATB2 downregulation are biological features for sessile serrated lesions and microvesicular hyperplastic polyps.

Sessile serrated lesions (SSLs) and microvesicular hyperplastic polyps (MVHPs) are colorectal lesions displaying gastric differentiation. Griffonia simplicifolia-II (GS-II) is a lectin specific to terminal α/ßGlcNAc residues. Here, we assessed GS-II binding and performed immunostaining for HIK1083 (specific to terminal αGlcNAc residues), MUC5AC, MUC6, and special AT-rich sequence binding protein 2 (SATB2) in SSLs, MVHPs, and tubular adenomas (TAs). We observed MUC5AC positivity in 28 of 30 SSLs, but in only three of 23 TAs. Moreover, 24 of 30 SSLs were MUC6-positive, while none of the 23 TAs were MUC6-positive. None of the 30 SSLs or 23 TAs showed HIK1083 positivity. All 30 SSLs and 26 MVHPs were GS-II-positive, while only seven of 23 were in TAs. GS-II staining was mainly distributed in the Golgi region, but SSLs and MVHPs showed goblet cell distribution, in 20 of 30 and 19 of 26 cases, respectively. All SSLs, MVHPs, and TAs were SATB2-positive, but 21 of 30 SSLs and 12 of 26 MVHPs showed decreased staining intensity relative to adjacent mucosa, a decrease seen in only two of 23 in TAs. These results indicate overall that increased terminal ßGlcNAc and decreased SATB2 expression are characteristics of SSLs and MVHPs.