To investigate the neurotoxicity profile of
glycidol and its effect on developmental hippocampal neurogenesis, pregnant Sprague Dawley rats were given
drinking water containing 0, 100, 300, or 1000 ppm
glycidol from gestational day 6 until weaning on day 21 after delivery. At 1000 ppm, dams showed progressively worsening gait abnormalities, and histopathological examination showed generation of neurofilament-L(+) spheroids in the cerebellar granule layer and dorsal funiculus of the medulla oblongata, central chromatolysis in the trigeminal nerve
ganglion cells, and axonal degeneration in the sciatic nerves. Decreased
dihydropyrimidinase-like 3(+) immature granule cells in the subgranular zone (SGZ) and increased immature reelin(+) or
calbindin-2(+) γ-
aminobutyric acid-ergic interneurons and neuron-specific
nuclear protein (NeuN)(+) mature neurons were found in the dentate hilus of the offspring of the 1000 ppm group on weaning. Hilar changes remained until postnatal day 77, with the increases in reelin(+) and NeuN(+) cells being present at ≥ 300 ppm, although the SGZ change disappeared. Thus,
glycidol caused axon injury in the central and peripheral nervous systems of adult rats, suggesting that
glycidol targets the newly generating nerve terminals of immature granule cells, resulting in the suppression of late-stage hippocampal neurogenesis. The sustained hilar changes may be a sign of continued aberrations in neurogenesis and migration. The no-observed-adverse-effect level was determined to be 300 ppm (48.8mg/kg
body weight/day) for dams and 100
ppm (18.5mg/kg
body weight/day) for offspring. The sustained developmental exposure effect on offspring neurogenesis was more sensitive than the adult axonal injury.