Abstract
Objective To explore whether prenatal stress promotes formation of chronic stressinduced hippocampal amyloid β (Aβ) protein in 6-month-old male offspring mice and its mechanism. Methods The APPswe/PS1dE9 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 of amyloid-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). 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. Key words: 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
Published Version
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