@article{ec70bc95beb949359156ef11bfd7b751,
title = "Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation",
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:",
author = "Jing Wang and Denis Gallagher and Devito, {Loren M.} and Cancino, {Gonzalo I.} and David Tsui and Ling He and Keller, {Gordon M.} and Frankland, {Paul W.} and Kaplan, {David R.} and Miller, {Freda D.}",
note = "Funding Information: The authors would like to thank Dennis Aquino, Sibel Naska, and Mark Gagliardi for technical support, advice, and discussions and Fred Wondisford for valuable insights and support. J.W. was supported by fellowships from the Multiple Sclerosis Society of Canada and the Three to Be Foundation, D.G. by a McEwen Center McMurrich fellowship, L.M.D. by an Alzheimer Society of Canada fellowship, G.I.C. by a Heart and Stroke Foundation of Canada fellowship, and D.T. by a CIHR Michael Smith studentship. P.W.F., D.R.K., and F.D.M. are Canada Research Chairs. This work was supported by funding from the CIHR (MOP86762 and MOP13958), the McEwen Center for Regenerative Medicine, the Canadian Stem Cell Network, and the Three to Be Foundation. ",
year = "2012",
month = jul,
day = "6",
doi = "10.1016/j.stem.2012.03.016",
language = "English (US)",
volume = "11",
pages = "23--35",
journal = "Cell stem cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}