Affiliation:
1. Innovative Institute
of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
2. School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
3. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
Abstract
Background:
Alzheimer's disease is the most common form of dementia, affecting millions
of people worldwide.
Methods:
Here, we analyzed the effects of metformin on APP/PS1 transgenic mice by behavioral test
and single-cell sequencing.
Results:
It showed that metformin can improve the spatial learning, memory function, and anxiety
mood of APP/PS1 transgenic mice. We identified transcriptionally distinct subpopulations of nine
major brain cell types. Metformin increased the differentiation of stem cells, decreased the proportion
of cells in the G2 phase, enhanced the generation of neural stem cells and oligodendrocyte progenitor
cells, and the tendency of neural stem cells to differentiate into astrocytes. Notably, 253 genes expressed
abnormally in APP/PS1 transgenic mice and were reversed by metformin. Ttr, Uba52, and
Rps21 are the top 3 genes in the cell-gene network with the highest node degree. Moreover, histochemistry
showed the expressions of RPS15, Uba52, and RPL23a were consistent with the data from
single-cell sequencing. Pathway and biological process enrichment analysis indicated metformin was
involved in nervous system development and negative regulation of the apoptotic process.
Conclusion:
Overall, metformin might play an important role in the differentiation and development
and apoptotic process of the central nervous system by regulating the expression of Ttr, Uba52,
Rps21, and other genes to improve cognition of APP/PS1 transgenic mice. These results provided a
clue for elaborating on the molecular and cellular basis of metformin on AD.
Funder
Natural Science Foundation of Shandong Province
Publisher
Bentham Science Publishers Ltd.
Subject
Neurology (clinical),Neurology
Cited by
1 articles.
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