Prenatal stress promotes formation of chronic stress-induced hippocampal amyloid β protein in offspring mice
10.3760/cma.j.issn.1671-8925.2015.08.009
- VernacularTitle:产前应激促进慢性应激诱导的子代鼠海马β-淀粉样蛋白形成
- Author:
Zhengyu WANG
1
;
Zhenmin HAN
;
Wei TANG
;
Yuyou YAO
Author Information
1. 安徽医科大学公共卫生学院
- Keywords:
Prenatal stress;
Chronic stress;
Eukaryotic initiation factor 2α;
Protein kinase R [PKR]-like ER kinase;
Glucose-regulated protein 78;
Beta-site APP-cleaving enzyme 1
- From:
Chinese Journal of Neuromedicine
2015;14(8):799-804
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether prenatal stress promotes formation of chronic stress-induced hippocampal amyloid β (Aβ) protein in 6-month-old male offspring mice and its mechanism.Methods The APPswe/PSIdE9 double transgenic mice were divided into 4 groups according to the prenatal stress and offspring mice stress:prenatal control-offspring control group (CC group),prenatal control-chronic offspring stress group (CT group),chronic prenatal stress-offspring control group (TC group),and chronic prenatal stress-chronic offspring stress group (TT group) (n=18).The number of amyloid plaques in brains was checked using Congo red staining.ELISA was used to examine the hippocampus levels ofamyloid-β proteins (Aβ1-42 and Aβ1-40) in the offspring mice;β-site APP-cleaving enzyme 1 (BACE1) activity was detected using fluorospectrophotometry.Additionally,Western blotting were used to observe the expression levels of phosphorylated eukaryotic initiation factor 2α (p-eIF2α),phosphorylated protein kinase R [PKR]-like ER kinase (p-PERK),glucose-regulated protein 78 (Grp78) and β-site BACE1 in the hippocampus.Results As compared with that in the CC group,the number of amyloid plaques in brain in CT,TT and TC groups was increased.The expressions of p-eIF2α,p-PERK,Grp78,BACE1,Aβ1-40 and Aβ1-42 in the hippocampus of CT group were significantly increased as compared with those in the CC group (P＜0.05).The expressions of p-eIF2α,p-PERK,Grp78,BACE1,Aβ1-40 and Aβ1-42 in the hippocampus of TT group were further significantly increased as compared with those in the CT group (P＜0.05).There was no significant difference in BACE1 activity among the different groups (P＞0.05).Conclusion The prenatal stress can promote the formation of hippocampal Aβ protein induced by chronic stress in 6-month-old male offspring mice,whose mechanism may be that prenatal stress aggravates hippocampal neurons endoplasmic reticulum stress,activates the PERK,then causes eIF2 alpha phosphorylation,and finally promotes BACE1 expression.
