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Cell Stem Cell. 2012 Jul 6;11(1):23-35. doi: 10.1016/j.stem.2012.03.016.

Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation.

Author information

1
Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

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.

PMID:
22770240
DOI:
10.1016/j.stem.2012.03.016
[Indexed for MEDLINE]
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