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

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. Miller

Research output: Contribution to journalArticle

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. Video Abstract:

Original languageEnglish (US)
Pages (from-to)23-35
Number of pages13
JournalCell Stem Cell
Volume11
Issue number1
DOIs
StatePublished - Jul 6 2012

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Metformin
Neurogenesis
Neural Stem Cells
Reversal Learning
Adult Stem Cells
Nervous System
Rodentia
Pharmacology
Neurons
Spatial Memory
Water
Brain
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. / Wang, Jing; Gallagher, Denis; Devito, Loren M.; Cancino, Gonzalo I.; Tsui, David; He, Ling; Keller, Gordon M.; Frankland, Paul W.; Kaplan, David R.; Miller, Freda D.

In: Cell Stem Cell, Vol. 11, No. 1, 06.07.2012, p. 23-35.

Research output: Contribution to journalArticle

Wang, J, Gallagher, D, Devito, LM, Cancino, GI, Tsui, D, He, L, Keller, GM, Frankland, PW, Kaplan, DR & Miller, FD 2012, 'Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation', Cell Stem Cell, vol. 11, no. 1, pp. 23-35. https://doi.org/10.1016/j.stem.2012.03.016
Wang, Jing ; Gallagher, Denis ; Devito, Loren M. ; Cancino, Gonzalo I. ; Tsui, David ; He, Ling ; Keller, Gordon M. ; Frankland, Paul W. ; Kaplan, David R. ; Miller, Freda D. / Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. In: Cell Stem Cell. 2012 ; Vol. 11, No. 1. pp. 23-35.
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