Affiliations: [a] Department of Laboratory Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China | [b] Department of Clinical Laboratory Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, China | [c] Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, Anhui, China | [d] Hefei Meikang Medical Equipment Co., Ltd., Hefei, Anhui, China
Correspondence:
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Correspondence to: Yu-You Yao, MD, Department of Clinical Laboratory Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China. Tel./Fax: +86 551 63869179; E-mail: tangwei317822887@sina.com.
Note: [1] These authors contributed equally to this work.
Abstract: In Alzheimer’s disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of AβPP, Aβ42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of Aβ42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene.
