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. 2021 Apr;39(2):444-455.
doi: 10.1007/s12640-020-00294-x. Epub 2020 Oct 6.

Sirt7-p21 Signaling Pathway Mediates Glucocorticoid-Induced Inhibition of Mouse Neural Stem Cell Proliferation

Mohammed A H Alnoud  1 , Wen Chen  1 , Nana Liu  1 , Wei Zhu  1 , Jing Qiao  1 , Shujuan Chang  1 , Yukang Wu  1 , Shanshan Wang  1 , Yiwei Yang  1 , Qiaoyi Sun  1 , Jiuhong Kang  2
Affiliations

Sirt7-p21 Signaling Pathway Mediates Glucocorticoid-Induced Inhibition of Mouse Neural Stem Cell Proliferation

Mohammed A H Alnoud et al. Neurotox Res. 2021 Apr.

Erratum in

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.

Keywords: Dexamethasone; GR; Neural stem cells; Sirt7; p21.

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References

    1. Anacker C, Hen R (2017) Adult hippocampal neurogenesis and cognitive flexibility—linking memory and mood. Nat Rev Neurosci 18:335–346 - PubMed - PMC
    1. Bertoli C, Skotheim JM, De Bruin RA (2013) Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol 14:518–528 - PubMed - PMC
    1. Bose R, Moors M, Tofighi R, Cascante A, Hermanson O, Ceccatelli S (2010) Glucocorticoids induce long-lasting effects in neural stem cells resulting in senescence-related alterations. Cell Death Dis 1:e92–e92 - PubMed - PMC
    1. Cha HH, Cram EJ, Wang EC, Huang AJ, Kasler HG, Firestone GL (1998) Glucocorticoids stimulate p21 gene expression by targeting multiple transcriptional elements within a steroid responsive region of the p21 waf1/cip1 promoter in rat hepatoma cells. J Biol Chem 273:1998–2007 - PubMed
    1. Choy KHC, de Visser Y, Nichols NR, van den Buuse M (2008) Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory. Hippocampus 18:655–667 - PubMed

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