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

J Wang, D Gallagher, LM DeVito, GI Cancino, D Tsui… - Cell stem cell, 2012 - cell.com
J Wang, D Gallagher, LM DeVito, GI Cancino, D Tsui, L He, GM Keller, PW Frankland
Cell stem cell, 2012cell.com
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 …
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.
Video Abstract
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