文献类型：期刊文献

英文题名：Programming of a developmental imbalance in hypothalamic glutamatergic/GABAergic afferents mediates low basal activity of the hypothalamic-pituitary-adrenal axis induced by prenatal dexamethasone exposure in male offspring rats

作者：Lu, Juan[1,2,3];Li, Qiang[3];Xu, Dan[2,4];Liao, Yongbin[1];Wang, Hui[2,4]

第一作者：Lu, Juan

通信作者：Liao, YB[1];Wang, H[2]

机构：[1]Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Jiangmen 529000, Guangdong, Peoples R China;[2]Wuhan Univ, Sch Basic Med Sci, Dept Pharmacol, Wuhan 430071, Peoples R China;[3]Gansu Univ Chinese Med, Gansu Prov Hosp TCM, Lanzhou 730050, Gansu, Peoples R China;[4]Hubei Prov Key Lab Dev Originated Dis, Wuhan 430071, Peoples R China

第一机构：Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Jiangmen 529000, Guangdong, Peoples R China

通信机构：[1]corresponding author), Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Jiangmen 529000, Guangdong, Peoples R China;[2]corresponding author), Wuhan Univ, Basic Med Sch, Dept Pharmacol, Wuhan 430071, Hubei, Peoples R China.

年份：2020

卷号：331

起止页码：33

外文期刊名：TOXICOLOGY LETTERS

收录：;Scopus(收录号：2-s2.0-85085894137);WOS:【SCI-EXPANDED(收录号:WOS:000547337000004)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (No. 81660544, 81901468, 81430089 and 81673524), the National Key Research and Development Programme of China (No. 2017YFC1001300), the Major Technological Innovation Projects of Hubei Province (No. 2019ACA140) and Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University (No. TFJC2018001).

语种：英文

外文关键词：Dexamethasone; Programming; Low basal activity; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Glutamatergic/GABAergic afferents

摘要：This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20 similar to postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.