Metformin & Neurogenesis

Metformin Activates an Atypical PKC-CBP Pathway to Promote Neurogenesis and Enhance Spatial Memory Formation

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Cell Stem Cell, Volume 11, Issue 1, 23-35, 6 July 2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.stem.2012.03.016

Refers to: An Old Drug for New Ideas: Metformin Pro...

Authors

Jing Wang,Denis Gallagher,Loren M. DeVito,Gonzalo I. Cancino,David Tsui,Ling He,Gordon M. Keller,Paul W. Frankland,David R. Kaplan,Freda D. MillerSee Affiliations

• Highlights
• aPKCs ζ and ι play distinct roles in the neural precursor to neuron transition
• Metformin enhances mammalian neurogenesis via the aPKC-CBP pathway
• Metformin increases adult neurogenesis in vivo and enhances spatial memory

Summary

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.