Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8553491 | Toxicology Letters | 2018 | 28 Pages |
Abstract
Adverse intrauterine environments can increase susceptibility to neuropsychiatric diseases that are related to cognitive impairment. In this study, we observed the cognitive impairment of male offspring rats after prenatal dexamethasone exposure (PDE) and explored the associated intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously injected with 0.2 mg/kg d dexamethasone from gestational day 9 (GD9) to GD20. A cohort of the pregnant rat group was sacrificed on GD20, and the male fetal rats were collected. Another group of pregnant rats delivered their offspring naturally, and the male adult offspring rats were subjected to behavioural tests postnatally at 26 weeks and then sacrificed. The adult PDE male offspring rats exhibited cognitive impairment, decreased cell proliferation and increased cell apoptosis in the hippocampus, along with damaged synaptic plasticity and disrupted protein synthesis. Meanwhile, activation of GR and downregulation of the cAMP responsive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin receptor tyrosine B (TrkB) signalling pathway were found in the adult PDE offspring rats. Further examinations indicated consistent alterations to the fetal hippocampus by PDE. We concluded that PDE can cause cognitive impairment in adult male offspring rats. The mechanism may be associated with low-functional programming of the hippocampal CREB/BDNF/TrkB signalling pathway.
Keywords
CDK2NR2BNR2ANR1TrkBCDC42Rac1FKBP5SF-1CaMKIIDNMTsSGK1DNA methyltransferasesPDEBcl-2IUGRRhoAcyclin-dependent kinase-2mTORKi67prenatal dexamethasone exposureCREBBDNFERK1/2Igf1Aktcognitive impairmentBaxlong-term potentiationLTPgestation dayStarcell division cycle 42SynaptophysinSynapsin IgresInsulin like growth factor 1intrauterine growth retardationglucocorticoid responsive elementsBrain-derived neurotrophic factorB-cell lymphoma 2mammalian target of rapamycinpostnatal weekHippocampustropomyosin-related kinase Bcalmodulin-dependent protein kinase IIBcl-2 Associated X proteincAMP responsive element binding proteinSteroidogenic acute regulatory proteinprotein kinase BCaspase-3extracellular signal-regulated kinase 1 and 2glucocorticoid receptor
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Authors
Wanting Dong, Dan Xu, Zewen Hu, Xia He, Zijing Guo, Zhexiao Jiao, Ying Yu, Hui Wang,