Discovery of a Proneurogenic, Neuroprotective Chemical

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Jul 7

PMID 20603013

Citations 169

Authors

Andrew A Pieper

Shanhai Xie

Emanuela Capota

Sandi Jo Estill

Jeannie Zhong

Jeffrey M Long

Ginger L Becker

Paula Huntington

Shauna E Goldman

Ching-Han Shen

Maria Capota

Jeremiah K Britt

Tiina Kotti

Kerstin Ure

Daniel J Brat

Noelle S Williams

Karen S MacMillan

Jacinth Naidoo

Lisa Melito

Jenny Hsieh

Jef De Brabander

Joseph M Ready

Steven L McKnight

Affiliations

Soon will be listed here.

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:

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