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Developmental exposure to diacetoxyscirpenol reversibly disrupts hippocampal neurogenesis by inducing oxidative cellular injury and suppressed differentiation of granule cell lineages in mice.
- Source :
-
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2020 Feb; Vol. 136, pp. 111046. Date of Electronic Publication: 2019 Dec 10. - Publication Year :
- 2020
-
Abstract
- To investigate the developmental exposure effect of diacetoxyscirpenol (DAS) on postnatal hippocampal neurogenesis, pregnant ICR mice were provided a diet containing DAS at 0, 0.6, 2.0, or 6.0 ppm from gestational day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without DAS exposure. On PND 21, neural stem cells (NSCs) and all subpopulations of proliferating progenitor cells were suggested to decrease in number in the subgranular zone (SGZ) at ≥ 2.0 ppm. At 6.0 ppm, increases of SGZ cells showing TUNEL <superscript>+</superscript> , metallothionein-I/II <superscript>+</superscript> , γ-H2AX <superscript>+</superscript> or malondialdehyde <superscript>+</superscript> , and transcript downregulation of Ogg1, Parp1 and Kit without changing the level of double-stranded DNA break-related genes were observed in the dentate gyrus. This suggested induction of oxidative DNA damage of NSCs and early-stage progenitor cells, which led to their apoptosis. Cdkn2a, Rb1 and Trp53 downregulated transcripts, which suggested an increased vulnerability to DNA damage. Hilar PVALB <superscript>+</superscript> GABAergic interneurons decreased and Grin2a and Chrna7 were downregulated, which suggested suppression of type-2-progenitor cell differentiation. On PND 77, hilar RELN <superscript>+</superscript> interneurons increased at ≥ 2.0 ppm; at 6.0 ppm, RELN-related Itsn1 transcripts were upregulated and ARC <superscript>+</superscript> granule cells decreased. Increased RELN signals may ameliorate the response to the decreases of NSCs and ARC-mediated synaptic plasticity. These results suggest that DAS reversibly disrupts hippocampal neurogenesis by inducing oxidative cellular injury and suppressed differentiation of granule cell lineages. The no-observed-adverse-effect level of DAS for offspring neurogenesis was determined to be 0.6 ppm (0.09-0.29 mg/kg body weight/day).<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Animals
Animals, Suckling
Apoptosis drug effects
Body Weight drug effects
Cell Lineage drug effects
Cell Proliferation drug effects
Down-Regulation drug effects
Female
Hippocampus pathology
Male
Mice, Inbred ICR
Organ Size drug effects
Pregnancy
Reelin Protein
Cell Differentiation drug effects
Hippocampus drug effects
Mycotoxins toxicity
Neurogenesis drug effects
Oxidative Stress drug effects
Trichothecenes toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6351
- Volume :
- 136
- Database :
- MEDLINE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Publication Type :
- Academic Journal
- Accession number :
- 31836554
- Full Text :
- https://doi.org/10.1016/j.fct.2019.111046