PMID- 28555334
OWN - NLM
STAT- MEDLINE
DCOM- 20180816
LR  - 20180816
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 91
IP  - 12
DP  - 2017 Dec
TI  - Prenatal nicotine exposure induces HPA axis-hypersensitivity in offspring rats 
      via the intrauterine programming of up-regulation of hippocampal GAD67.
PG  - 3927-3943
LID - 10.1007/s00204-017-1996-8 [doi]
AB  - The intrauterine programming of hypothalamic-pituitary-adrenal (HPA) axis 
      hypersensitivity is associated with chronic adult diseases. Our previous studies 
      demonstrated the HPA-axis hypersensitivity in offspring rats induced by prenatal 
      nicotine exposure. The goal of the present study is to further investigate the 
      intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously 
      administered with 2.0 mg/kg day of nicotine from gestational day (GD) 9-20. A 
      group of the pregnant rats was euthanized at GD20, and the fetal rats were 
      extracted. The remaining rats were left to come to term, and the adult offspring 
      were exposed to chronic stress. For adult offspring rats, prenatal nicotine 
      exposure induced HPA-axis hypersensitivity after chronic stress, accompanied by 
      imbalanced glutamatergic/GABAergic afferent inputs. Moreover, prenatal nicotine 
      exposure enhanced the expression of hippocampal glutamic acid decarboxylase 67 
      (GAD67), accompanied by a decreased methylation ratio within nt -1019 to -689 of 
      the GAD67 promoter, decreased expression of Dnmt1, and an increased GABA content 
      and density of GABAergic neurons. The fetal rats exhibited changes consistent 
      with the adult rats. Similar effects were also observed by treating the fetal 
      hippocampal cell line H19-7 with 1-100 muM nicotine, while dihydro-beta-erythroidine 
      hydrobromide (DHbetaE), the specific inhibitor of alpha4beta2nAChR, can reverse the effects 
      caused by nicotine. These results indicate that prenatal nicotine exposure can 
      enhance the potential excitability of the hypothalamus via the intrauterine 
      programming of up-regulation of hippocampal GAD67. All of these results 
      contribute to the HPA-axis hypersensitivity in adult offspring.
FAU - He, Xia
AU  - He X
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Lu, Juan
AU  - Lu J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Dong, Wanting
AU  - Dong W
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Jiao, Zhexiao
AU  - Jiao Z
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Zhang, Chong
AU  - Zhang C
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Yu, Ying
AU  - Yu Y
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
FAU - Zhang, Zhaohui
AU  - Zhang Z
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China. xuyidan70188@whu.edu.cn.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China. xuyidan70188@whu.edu.cn.
LA  - eng
GR  - 81371483/National Natural Science Foundation of China/
GR  - 81220108026/National Natural Science Foundation of China/
GR  - 81430089/National Natural Science Foundation of China/
GR  - 81202240/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20170529
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (Dnmt1 protein, rat)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
RN  - W980KJ009P (Corticosterone)
SB  - IM
EIN - Arch Toxicol. 2017 Aug 3;:. PMID: 28776196
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Birth Weight
MH  - Corticosterone/blood
MH  - DNA (Cytosine-5-)-Methyltransferase 1/genetics
MH  - Epigenesis, Genetic
MH  - Female
MH  - Glutamate Decarboxylase/*genetics/metabolism
MH  - Hippocampus/*drug effects/embryology/physiology
MH  - Hypothalamo-Hypophyseal System/drug effects/*physiology
MH  - Nicotine/*toxicity
MH  - Pituitary-Adrenal System/drug effects/*physiology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats, Wistar
MH  - Up-Regulation/drug effects
MH  - gamma-Aminobutyric Acid/metabolism
OTO - NOTNLM
OT  - GAD67
OT  - HPA axis
OT  - Hippocampus
OT  - Hypothalamus
OT  - Nicotine
EDAT- 2017/05/31 06:00
MHDA- 2018/08/17 06:00
CRDT- 2017/05/31 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/05/18 00:00 [accepted]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2018/08/17 06:00 [medline]
PHST- 2017/05/31 06:00 [entrez]
AID - 10.1007/s00204-017-1996-8 [pii]
AID - 10.1007/s00204-017-1996-8 [doi]
PST - ppublish
SO  - Arch Toxicol. 2017 Dec;91(12):3927-3943. doi: 10.1007/s00204-017-1996-8. Epub 
      2017 May 29.