Notch1-mediated aerobic exercise promotes hippocampal nerve cell proliferation in Alzheimer’s disease mice

doi:10.12307/2024.181

Abstract

Abstract: BACKGROUND: Abnormal Notch1 signaling pathway is mostly found in the brain of Alzheimer’s disease patients, but the role of these signaling pathways in the pathogenesis of Alzheimer’s disease has not been fully clarified. Long-term aerobic exercise can alter the expression of Notch1 by affecting the methylation rate of factors related to the Notch1 signaling pathway. However, it is not clear whether aerobic exercise affects hippocampal nerve cell proliferation and histopathological features of Alzheimer’s disease mice through the Notch1 signaling pathway.
OBJECTIVE: To observe the effects of aerobic exercise on the proliferation and histopathological features of hippocampal nerve cells in Alzheimer’s disease mice after DAPT inhibited the Notch1 signaling pathway.
METHODS: APP/PS1 double transgenic Alzheimer’s disease mice aged 3 months were randomly divided into four groups: control group, exercise control group, inhibitor group, and exercise inhibitor group, with 20 mice in each group. The control group was fed naturally, and the exercise group received aerobic exercise intervention. Both natural feeding and exercise intervention lasted for 20 weeks. The mice were injected with solvent or Notch1 inhibitor at week 18. After 20 weeks, the brain tissue was collected, and Aβ1-42, Tau, Ki67, and Notch1 expression levels were detected by real-time PCR, immunofluorescence, and western blot assay.
RESULTS AND CONCLUSION: Compared with the control group, the expressions of Ki67 and Notch1 in the dentate gyrus region of the hippocampus were significantly decreased in the inhibitor group (P < 0.05), but there were no significant differences in Aβ1-42 and Tau. The expression of Ki67 in the dentate gyrus region of the hippocampus in the exercise control group was significantly higher than that in the control group, while the expressions of Aβ1-42, Tau, and Notch1 were significantly lower than those in the control group (P < 0.05). The expressions of Aβ1-42, Tau, Ki67, and Notch1 in the dentate gyrus region of the hippocampus of the exercise inhibitor group were not significantly different from those of the inhibitor group. In conclusion, the Notch1 signaling pathway may mediate exercise to improve the proliferation and histopathological features of hippocampal nerve cells in Alzheimer’s disease mice.

Key words: Alzheimer’s disease, aerobic exercise, Notch1, nerve cell proliferation

CLC Number:

Li Huijun, Li Chuikun, Wei Cuilan, Zhang Yeting. Notch1-mediated aerobic exercise promotes hippocampal nerve cell proliferation in Alzheimer’s disease mice[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(31): 4951-4957.

Figures/Tables 12

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