Metformin Activates an Atypical PKC-CBP Pathway to Promote Neurogenesis and Enhance Spatial Memory Formation
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Video abstract Although endogenous recruitment of adult neural stem cells has been proposed as a therapeutic strategy, clinical approaches for achieving this are lacking. Here, we show that metformin, a widely used drug, promotes neurogenesis and enhances spatial memory formation. Specifically, we show that an atypical PKC-CBP pathway is essential for the normal genesis of neurons from neural precursors and that metformin activates this pathway to promote rodent and human neurogenesis in culture. Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent fashion, and in so doing enhances spatial reversal learning in the water maze. Thus, metformin, by activating an aPKC-CBP pathway, recruits neural stem cells and enhances neural function, thereby providing a candidate pharmacological approach for nervous system therapy.
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Metformin promotes rodent and human neurogenesis in culture by activating the PKC-CBP pathway, recruiting neural stem cells, and enhancing neural function, particularly spatial memory.
“Metformin has been shown to promote rodent and human neurogenesis in culture by activating a protein kinase C-CREB binding protein (PKC-CBP) pathway, recruiting neural stem cells and enhancing neural function, particularly spatial memory function.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [132]
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- Authors
- Wang, J., Gallagher, D., DeVito, L. M., Cancino, G. I., Tsui, D., He, L., Keller, G. M., Frankland, P. W., Kaplan, D. R., & Miller, F. D.
- Affiliations
- Hospital for Sick Children (CA)
- University Health Network (CA)
- University of Toronto (CA)
- Johns Hopkins University (US)
- Corresponding author
- Miller, Freda D.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 11
- Issue
- 1
- Pages
- 23-35
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2128367294
- Cited by
- 474
- References
- 28
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 34 · 2023: 29 · 2022: 37 · 2021: 34 · 2020: 50 · 2019: 59 · 2018: 38 · 2017: 29 · 2016: 36 · 2015: 28 · 2014: 29 · 2013: 27 · 2012: 11
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP13958, MOP- 86762)
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK085142)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, protein kinase C, CBP, atypical PKC, neurogenesis, adult neural stem cells, spatial memory, spatial learning, neuronal precursors, water maze
- MeSH terms
- Aging, Animals, Cell Differentiation, Cerebral Cortex, Enzyme Activation, Hippocampus, Humans, Isoenzymes, Memory, Metformin, Neurons, Olfactory Bulb, Protein Kinase C, Signal Transduction, CREB-Binding Protein, Mice, Embryonic Stem Cells, Neurogenesis, Gene Knockdown Techniques, Neural Stem Cells
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