Neuroprotective and Neurogenesis-enhancing Effects of Sodium Ferulate

Abstract: Antidepressants with novel targets and without side effects are in great demand. Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity， and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA (or SF) show significant protective effect on excitotoxicity and antidepressant-like effect， and we now test the neuroprotective and neurogenesis-enhancing actions of SF and discuss their relationship with its antidepressant-like effect of SF. MTT assay was performed to measure the effect of SF on the growth of PC12 cells and its neuroprotective effects; morphological and immunocytochemical methods were used for assessing its differentiation-inducing action. The expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the proliferation of neural stem cell/neural progenitor cells were assessed in the hippocampi of chronic mild stress (CMS)-induced depression-like model rats by immunohistochemistry and BrdU-incorporation assays. In vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5~320 mmol/L， and partially protected PC12 cells against H2O2-induced oxidative and dexamethasone (DXM)-induced neurotoxicity damage， and induced PC12 cells to differentiate to more mature cells with the morphological characteristics and molecular marker of neuronal-like cells. In vivo tests showed that SF up-regulated the expressions of NGF and BDNF， and induced the proliferation of neural stem cell/neural progenitor cells in the hippocampi of CMSinduced depression-like model rats. This study provides evidences that SF shows the neuroprotective and neurogenesisenhancing actions， and the antidepressant-like effects of SF may result from its neuroprotective and neurogenesisenhancing actions.

CSTR: 32200.14.cjcb.2010.06.0002