Maternal exposure to ochratoxin A targets intermediate progenitor cells of hippocampal neurogenesis in rat offspring via cholinergic signal downregulation and oxidative stress responses
| Autor: | Yumi Kangawa, Yasuko Hasegawa-Baba, Makoto Shibutani, Toshinori Yoshida, Sayaka Mizukami, Takeshi Tanaka, Yousuke Watanabe |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Doublecortin Protein Offspring Neurogenesis Down-Regulation Hippocampal formation Biology Toxicology Hippocampus Subgranular zone Rats Sprague-Dawley 03 medical and health sciences Neural Stem Cells Pregnancy Internal medicine medicine Animals Progenitor cell Maternal-Fetal Exchange No-Observed-Adverse-Effect Level Dentate gyrus Ochratoxins Oxidative Stress 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Prenatal Exposure Delayed Effects biology.protein GABAergic Female Neurotrophin |
| Zdroj: | Reproductive toxicology (Elmsford, N.Y.). 65 |
| ISSN: | 1873-1708 |
| Popis: | To elucidate the developmental exposure effects of ochratoxin A (OTA) on postnatal hippocampal neurogenesis, pregnant SD rats were provided a diet containing 0, 0.12, 0.6, or 3.0ppm OTA from gestation day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without OTA exposure. At 3.0ppm, offspring of both sexes showed a transient body weight decrease after weaning. Changes in hippocampal neurogenesis-related parameters as measured in male PND 21 offspring were observed at 3.0ppm. In the subgranular zone (SGZ) of the dentate gyrus, PAX6+ or TBR2+ cells were decreased, while GFAP+ or DCX+ cells did not fluctuate in number, suggesting decreased numbers of type-2 progenitor cells. On the other hand, SGZ cells accumulating malondialdehyde increased. In the hilus of the dentate gyrus, SST+ or CHRNB2+ γ-aminobutyric acid (GABA)-ergic interneurons decreased, accompanied with transcript downregulation of Chrnb2 in the dentate gyrus. These results suggest that maternal exposure to OTA decreased type-2 progenitor cells by reducing hilar GABAergic interneurons innervating type-2 progenitor cells via cholinergic signal downregulation and also by increasing oxidative stress in the SGZ. Transcript levels of neurotrophin (Bdnf), glutamatergic receptors (Gria1, Gria2, and Grin2a), serotonin-synthesizing enzyme, and serotonergic receptors (Tph2, Htr1a, and Htr4) increased in the dentate gyrus, suggesting multiple neuroprotective actions against OTA-induced aberrant neurogenesis. All observed fluctuations were reversed by PND 77. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.6ppm, corresponding to 39.3-76.0μg/kg body weight/day. |
| Databáze: | OpenAIRE |
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