PMID- 29111458
OWN - NLM
STAT- MEDLINE
DCOM- 20180104
LR  - 20200930
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 283
DP  - 2018 Feb
TI  - Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive 
      impairment in male offspring after prenatal dexamethasone exposure.
PG  - 1-12
LID - S0378-4274(17)31443-1 [pii]
LID - 10.1016/j.toxlet.2017.10.020 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Dong, Wanting
AU  - Dong W
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China.
FAU - Xu, Dan
AU  - Xu D
AD  - 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.
FAU - Hu, Zewen
AU  - Hu Z
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China.
FAU - He, Xia
AU  - He X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China.
FAU - Guo, Zijing
AU  - Guo Z
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China.
FAU - Jiao, Zhexiao
AU  - Jiao Z
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China.
FAU - Yu, Ying
AU  - Yu Y
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 
      430071, China; Department of Neurology, Renmin Hospital of Wuhan University, 
      Wuhan 430060, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan 430071, China.
LA  - eng
PT  - Journal Article
DEP - 20171027
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Anxiety/psychology
MH  - Apoptosis/drug effects
MH  - Behavior, Animal/drug effects
MH  - Body Weight/drug effects
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics
MH  - Cell Proliferation/drug effects
MH  - Cognitive Dysfunction/*chemically induced/*genetics
MH  - Cyclic AMP Response Element-Binding Protein/biosynthesis/genetics
MH  - Dexamethasone/blood/*toxicity
MH  - Exploratory Behavior/drug effects
MH  - Female
MH  - Fetal Development/*drug effects
MH  - Hippocampus/pathology
MH  - Male
MH  - Maze Learning/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*genetics/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/biosynthesis/genetics
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Cognitive impairment
OT  - Glucocorticoid receptor
OT  - Hippocampus
OT  - Pregnancy dexamethasone exposure
EDAT- 2017/11/08 06:00
MHDA- 2018/01/05 06:00
CRDT- 2017/11/08 06:00
PHST- 2017/06/11 00:00 [received]
PHST- 2017/10/19 00:00 [revised]
PHST- 2017/10/26 00:00 [accepted]
PHST- 2017/11/08 06:00 [pubmed]
PHST- 2018/01/05 06:00 [medline]
PHST- 2017/11/08 06:00 [entrez]
AID - S0378-4274(17)31443-1 [pii]
AID - 10.1016/j.toxlet.2017.10.020 [doi]
PST - ppublish
SO  - Toxicol Lett. 2018 Feb;283:1-12. doi: 10.1016/j.toxlet.2017.10.020. Epub 2017 Oct 
      27.