@article{dfe39a035eec45e58e56a77df8024c1d,
title = "Discovery of a Proneurogenic, Neuroprotective Chemical",
abstract = "An in vivo screen was performed in search of chemicals capable of enhancing neuron formation in the hippocampus of adult mice. Eight of 1000 small molecules tested enhanced neuron formation in the subgranular zone of the dentate gyrus. Among these was an aminopropyl carbazole, designated P7C3, endowed with favorable pharmacological properties. In vivo studies gave evidence that P7C3 exerts its proneurogenic activity by protecting newborn neurons from apoptosis. Mice missing the gene encoding neuronal PAS domain protein 3 (NPAS3) are devoid of hippocampal neurogenesis and display malformation and electrophysiological dysfunction of the dentate gyrus. Prolonged administration of P7C3 to npas3-/- mice corrected these deficits by normalizing levels of apoptosis of newborn hippocampal neurons. Prolonged administration of P7C3 to aged rats also enhanced neurogenesis in the dentate gyrus, impeded neuron death, and preserved cognitive capacity as a function of terminal aging. PaperClip:",
keywords = "Chembio, Molneuro",
author = "Pieper, {Andrew A.} and Shanhai Xie and Emanuela Capota and Estill, {Sandi Jo} and Jeannie Zhong and Long, {Jeffrey M.} and Becker, {Ginger L.} and Paula Huntington and Goldman, {Shauna E.} and Shen, {Ching Han} and Maria Capota and Britt, {Jeremiah K.} and Tiina Kotti and Kerstin Ure and Brat, {Daniel J.} and Williams, {Noelle S} and MacMillan, {Karen S.} and Jacinth Naidoo and Lisa Melito and Jenny Hsieh and {De Brabander}, {Jef K} and Ready, {Joseph M} and McKnight, {Steven L}",
note = "Funding Information: We thank the Wang lab for extensive help in establishing the live-cell imaging assay used to measure mitochondrial membrane permeability; Xiaodong Wang and Sol Snyder for invaluable scientific input; Patrick Harran for helping select the 1000 chemicals chosen for in vivo screening; David Russell and members of the Russell lab for extensive help in electrophysiological recording assays; Christopher Cowan and members of the Cowan laboratory for assistance with primary neuronal cultures; Farah Veerjee, Saira Hussein, Latisha McDaniel, Ruth Starwalt, and Leeju Wu for technical assistance; and Huda Zoghbi, Sol Snyder, Joe Goldstein, Ueli Schibler, Al Gilman, Mike Brown, Richard Axel, and Martin Raff for critical review of the manuscript. We thank Angela Diehl for help with the graphical abstract artwork. This work was supported by grants from The Hartwell Foundation, Staglin Family fund, University of Texas Southwestern Medical Center High Risk/High Impact research fund, National Alliance for Research on Schizophrenia and Depression, and Morton H. Meyerson Family Tzedakah Fund awarded to A.A.P.; a Transformative RO1 grant (National Institute of Mental Health [NIMH] 1RO1MH087986) awarded to A.A.P. and S.L.M.; and a National Institutes of Health (NIH) Pioneer grant (National Institute of General Medical Sciences 5DP1OD000276), an NIH Method to Extend Research in Time grant (NIMH RO1MH59388), a National Cancer Institute Program Project Grant (5PO1CA95471), a Simons Foundation Autism Research Initiative grant from the Simons Foundation, and funds from an anonymous donor provided to S.L.M. ",
year = "2010",
month = jul,
doi = "10.1016/j.cell.2010.06.018",
language = "English (US)",
volume = "142",
pages = "39--51",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}