Abstract:
:Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that DEX inhibited cell proliferation and Sirt7 expression. In addition, prenatal mouse overexposure to DEX induced the suppression of Sirt7 in the hippocampus of offspring. Sirt7 knockdown significantly decreased the percentage of proliferating cells but did not further reduce the NSC proliferation rate in the presence of DEX, whereas Sirt7 overexpression rescued DEX-induced inhibition of hippocampal NSC proliferation. Moreover, DEX inhibited Sirt7 expression through the glucocorticoid receptor (GR), and p21 was found to mediate the functional effect of DEX-induced Sirt7 suppression. In conclusion, our data demonstrate for the first time the effect of DEX on the Sirt7-p21 pathway in hippocampal NSCs, identifying a new potential therapeutic target for prenatal GC overexposure-related neurodevelopmental disorders in offspring.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Alnoud MAH,Chen W,Liu N,Zhu W,Qiao J,Chang S,Wu Y,Wang S,Yang Y,Sun Q,Kang Jdoi
10.1007/s12640-020-00294-xsubject
Has Abstractpub_date
2020-10-06 00:00:00eissn
1029-8428issn
1476-3524pii
10.1007/s12640-020-00294-xpub_type
杂志文章abstract::Mercury is a toxic metal shown to have harmful effects on human health. Several studies have reported high blood mercury concentrations as a risk factor for autism spectrum disorders (ASDs), while other studies have reported no such association. The goal of this study was to investigate the association between blood m...
journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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doi:10.1007/s12640-016-9652-2
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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