Journal
CELL
Volume 142, Issue 1, Pages 39-51Publisher
CELL PRESS
DOI: 10.1016/j.cell.2010.06.018
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Funding
- 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
- Morton H. Meyerson Family Tzedakah Fund
- National Institute of Mental Health [NIMH] [RO1, 1RO1MH087986]
- National Institutes of Health (NIH)
- National Institute of General Medical Sciences [5DP1OD000276]
- NIH Method to Extend Research [NIMH RO1MH59388]
- National Cancer Institute Program [5PO1CA95471]
- Simons Foundation Autism Research
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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.
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