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.
Yabe
T
T
Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan. tyabe@lisci.kitasato-u.ac.jp
Hirahara
H
H
Harada
N
N
Ito
N
N
Nagai
T
T
Sanagi
T
T
Yamada
H
H
D000375:Aging; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology; D003373:Coumaric Acids / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000209:etiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy; D013687:Telencephalon / Q000187:drug effects / Q000502:physiology
D002491:Central Nervous System Agents; D003373:Coumaric Acids; C004999:ferulic acid; D003345:Corticosterone