Treffer: Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive impairment in male offspring after prenatal dexamethasone exposure.

Title:
Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive impairment in male offspring after prenatal dexamethasone exposure.
Authors:
Dong W; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China., Xu D; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: xuyidan70188@whu.edu.cn., Hu Z; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China., He X; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China., Guo Z; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China., Jiao Z; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China., Yu Y; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China., Wang H; Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
Source:
Toxicology letters [Toxicol Lett] 2018 Feb; Vol. 283, pp. 1-12. Date of Electronic Publication: 2017 Oct 27.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE
Imprint Name(s):
Publication: Amsterdam : Elsevier
Original Publication: Amsterdam, Elsevier/North Holland.
MeSH Terms:
Cognitive Dysfunction/*chemically induced , Cognitive Dysfunction/*genetics , Dexamethasone/*toxicity , Fetal Development/*drug effects , Prenatal Exposure Delayed Effects/*genetics , Signal Transduction/*drug effects, Animals ; Anxiety/psychology ; Apoptosis/drug effects ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Brain-Derived Neurotrophic Factor/biosynthesis ; Brain-Derived Neurotrophic Factor/genetics ; Cell Proliferation/drug effects ; Cyclic AMP Response Element-Binding Protein/biosynthesis ; Cyclic AMP Response Element-Binding Protein/genetics ; Dexamethasone/blood ; Exploratory Behavior/drug effects ; Female ; Hippocampus/pathology ; Male ; Maze Learning/drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects/pathology ; Rats ; Rats, Wistar ; Receptor, trkB/biosynthesis ; Receptor, trkB/genetics
Contributed Indexing:
Keywords: Brain-derived neurotrophic factor; Cognitive impairment; Glucocorticoid receptor; Hippocampus; Pregnancy dexamethasone exposure
Substance Nomenclature:
0 (Brain-Derived Neurotrophic Factor)
0 (Cyclic AMP Response Element-Binding Protein)
7S5I7G3JQL (Dexamethasone)
EC 2.7.10.1 (Ntrk2 protein, rat)
EC 2.7.10.1 (Receptor, trkB)
Entry Date(s):
Date Created: 20171108 Date Completed: 20180104 Latest Revision: 20200930
Update Code:
20250114
DOI:
10.1016/j.toxlet.2017.10.020
PMID:
29111458
Database:
MEDLINE

Weitere Informationen

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 0.2mg/kgd 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.
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