Curcumin Promotes Proliferation of Adult Neural Stem Cells and the Birth of Neurons in Alzheimer's Disease Mice via Notch Signaling Pathway

The abnormal deposition of amyloid-beta peptide, a major component of senile plaques, has been reported to be the major cause of neuronal cell death and cognitive impairment in Alzheimer's disease (AD). Adult neurogenesis is related to the amelioration of impaired neurons and cognitive impairment. In the research, we investigated the function of curcumin on endogenous neural stem cells (NSCs) and hippocampal neurogenesis in mice. APP/PS1 transgenic mice as animal models were treated with curcumin, and a significant improvement in learning and memory function was observed. The improvement was associated with a significant increase in the number of new neural stem cells (BrdU(+)/Nestin(+)) and newborn neurons (NeuN/kI67(+)) in the hippocampal region and decreased the number of apoptotic neurons (TUNEL+ and Caspase-3/NeuN(+)). These results suggested that curcumin activated NSCs proliferation, improved neurogenesis, and ameliorated cognitive impairment of AD mice. Then, we identified that curcumin upregulated the expression of self-renewal genes, Notch1 and Hes1, and augmentation of CDK4, Cyclin D1, NICD, and Hes1 protein. As Notch activity was blocked by the DAPT, the related proteins were downregulated, and the initiating cell proliferation of curcumin was abolished. These results might suggest that the function of curcumin was dependent on Notch signaling pathway.