FERULIC ACID INDUCES NEURAL PROGENITOR CELL PROLIFERATION IN VITRO AND IN VIVO

Ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA) is a plant constituent and is contained in several medicinal plants for clinical use. In this paper, we investigated the effects of FA on the proliferation of neural stem/progenitor cells (NSC/NPCs) in vitro and in vivo. FA significantly increased the proliferation of NSC/NPCs cultured from the telencephalon of embryonic day-14 rats, and increased the number and size of secondary formed neurospheres. An in vitro differentiation assay showed that FA did not affect the percentage of either neuron-specific class III beta-tubulin (Tuj-1)-positive cells or glial fibrillary acidic protein (GFAP)-positive cells in the total cell population. Oral administration of FA increased the number of newly generated cells in the dentate gyrus (DG) of the hippocampus of corticosterone (CORT)treated mice, indicating that FA enhances the proliferation of adult NSC/NPCs in vivo. We also found that oral administration of FA increased cAMP response element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) mRNA level in the hippocampus of CORT-treated mice, and ameliorated the stress-induced depression-like behavior of mice. These novel pharmacological effects of FA may be useful for the treatment of mood disorders such as depression. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.