Chronic Prenatal Stress Exacerbates Learning And Memory Impairment In Adult Offspring Mice Who Also Suffer Chronic Stress And Its Related Mechanisms

Objective: To determine whether chronic prenatal stress could exacerbate learning and memory impairment in 6-month-old male APPswe/PS1 d E9 offspring mice who also suffer chronic stress, and if so, what the underlying mechanism is.Methods: There were four groups: the prenatal control-offspring control group(CC group), the prenatal control-chronic offspring stress group(CT group), the chronic prenatal stress-offspring control group(TC group), and the chronic prenatal stress-chronic offspring stress group(TT group). Morris water maze was used to investigate learning and memory impairment in mice. HE stain was used to observe the histopathologic changes in CA3 field of the hippocampus. Immunohistochemistry(IHC) technique was used to semi-quantitatively detect the in-situ expression stastus of amyloid precursor protein(APP), β-site APP-cleaving enzyme 1(BACE1) and amyloid β-peptide protein 1-42(Aβ42) in CA3 field of the hippocampus. Congo red stain was used to examine the amyloid deposits in mice brain tissue. Western blot was used to quantitatively detect the expression levels of APP, BACE1 and Aβ42 in mice hippocampus tissue. Additionally, we also used ELISA to examine the serum levels of corticosterone in the offspring mice.Results: Compared with the CC group, the results showed that CT group mice had more escape latency and swimming distance(P<0.05), less number of crossing the platform site and swimming time in the quadrant of the platform(P < 0.05).Furthermore, the neuropathological changes were characterized by the disintegrated pyramidal layered structure, decreased neuron number, worse cell morphology, soma condensation, nuclear pyknosis in the CA3 field of hippocampus in the CT group(P<0.05). Moreover, the expression of APP, BACE1 and Aβ42 in hippocampus were increased, as well as the serum corticosterone concentration in the CT group(P<0.05). Noteworthy, the learning and memory impairment and neuropathological changes stated above were worse in TT group mice compared to CT group mice(P<0.05).Conclusion: Chronic stress could exacerbate learning and memory impairment in offspring mice who also suffer chronic stress, which may be related to chronic prenatal stress potentiate the production of Aβ42 mediated by glucocorticoids through increasing expression of APP and BACE1 gene.