Journal
CELL STEM CELL
Volume 11, Issue 1, Pages 23-35Publisher
CELL PRESS
DOI: 10.1016/j.stem.2012.03.016
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Funding
- Multiple Sclerosis Society of Canada
- Three to Be Foundation
- McEwen Center
- Alzheimer Society
- Heart and Stroke Foundation of Canada
- CIHR [MOP86762, MOP13958]
- McEwen Center for Regenerative Medicine
- Canadian Stem Cell Network
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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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