Research Paper Volume 16, Issue 10 pp 9168—9187

Chronic stress induces Alzheimer’s disease-like pathologies through DNA damage-Chk1-CIP2A signaling

class="figure-viewer-img"

Figure 4. Vitamin C and Chk1 inhibitor reduce DNA damage, Chk1 activation and CIP2A expression, decrease tau phosphorylation and Aβ levels in hippocampus of mice exposed to chronic stress. (A) Representative immunoblots of γH2A.X, Chk1-pS317, Chk1-pS345, Chk1, CIP2A, β-actin in hippocampal tissues of mice in different groups. (B) Quantification of the relative protein levels; non-phosphorylated proteins such as γH2A.X and CIP2A were normalized to the β-actin levels; phosphorylated Chk1-pS317, Chk1-pS345 were normalized to total Chk1. n = 3 per group. (C) Representative immunoblots of Tau-pT231, Tau-pS396, Tau-pS404, Tau-5, APP-pT668, APP, β-actin in hippocampus of mice in different groups. (D) Quantification of the relative protein expression levels; phosphorylated Tau-pT231, Tau-pS396, Tau-pS404 and APP-pT668 were normalized to Tau-5 and total APP respectively. n = 3 per group. (E) The Aβ40 and Aβ42 in soluble fraction of hippocampal tissues in different groups were detected by ELISA kit. n = 3 per group. (F) The Aβ40 and Aβ42 in insoluble fraction of hippocampal tissues in different groups were detected by ELISA kit. n = 3 per group. All data represent mean ± SEM *P<0.05, **P<0.01, ***P < 0.001, ****P < 0.0001.