Neurogenesis-enhancing effect of sodium ferulate and its role in repair following stress-induced neuronal damage

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 shows neuroprotective effect and significant antidepressantlike effect. The aim of this study was to investigate its potential neurogenesis-enhancing effect and its role in repair following stress-induced neuronal damage. MTT assay was performed to measure the effect of SF on the growth of rat pheochromocytoma (PC12) cells; morphological and immunocytochemical methods were used for assessing its differentiation-inducing action. Chronic mild stress (CMS) tests were performed to establish rat model of depression. The histopathology of animal brains was studied to analyze CMS-induced morphological changes and the effect of SF on the repair of CMS-induced brain injury. 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 bromodeoxyuridine (BrdU)incorporation assays, respectively. Our in vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5 320 μM, 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 CMS-induced depression-like model rats. This study provides evidences that SF shows neurogenesis-enhancing effect, and its antidepressant-like effect of SF may be related directly and closely to its above-mentioned effect.