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Antidepressant-like Effect of Cell-free Filtrate of Sodium Ferulate-induced and Differentioned PC12 Cell Lysates
Ming-Neng Liao1, Li-Jian Yu1*, Yong-Ping Zhang1, Run-Di Ma1*, Xiao-Yu Zhang1,3, Ting-Xi Yu1,2*
1Key Laboratory of Marine Materia Medica, Guangdong Ocean University, Zhanjiang 524025, China; 2Cell Biology Group, Department of Surgery, Department of Pathology, University of Maryland School of Medicine and Baltimore Veterans Affa
Abstract: Ferulic acid (FA)， 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid， is one of the most common phenolic acids with low toxicity， and sodium ferulate (SF) is its sodium salt. Our previous work demonstrates that SF has significant neuroprotective and neurogenesis-enhancing actions and antidepressant-like effects. The aim of this study was to investigate a potential antidepressant-like effect of cell-free filtrate of sodium ferulate-induced and differentioned PC12 cell lysates (SFIDPC12CL) in the chronic mild stress (CMS)-induced depression-like model rats. PC12 cells were cultured in DMEM containing 80 μmol/L SF for 6 days， and then cell-free SFIDPC12CL
was prepared. Residual SF concentration in cell-free SFIDPC12CL was assayed by HPLC. Depressionlike rat models were reproduced by CMS stimuli. Antidepressant effects of SFIDPC12CL were assessed by behavioural tests. The effects of SFIDPC12CL on hippocampal and cerebral cortex expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were assayed by immunohistochemistry， and the effect of SFIDPC12CL on hippocampal neurogenesis assayed using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells in CMS-induced depression-like model rats. Our studies demonstrate that administration of SFIDPC12CL significantly attenuated the CMS-induced depression-like behavioural disorders， up-regulated the hippocampal and cerebral cortex expressions of NGF and BDNF， and increased the hippocampal number of BrdUlabeled cells. These findings indicate that SFIDPC12CL shows marked antidepressant-like effects in the CMSinduced depression-like model rats， and raise the possibility that SFIDPC12CL up-regulates expressions of NGF and BDNF， and increases neuronal number.
was prepared. Residual SF concentration in cell-free SFIDPC12CL was assayed by HPLC. Depressionlike rat models were reproduced by CMS stimuli. Antidepressant effects of SFIDPC12CL were assessed by behavioural tests. The effects of SFIDPC12CL on hippocampal and cerebral cortex expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were assayed by immunohistochemistry， and the effect of SFIDPC12CL on hippocampal neurogenesis assayed using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells in CMS-induced depression-like model rats. Our studies demonstrate that administration of SFIDPC12CL significantly attenuated the CMS-induced depression-like behavioural disorders， up-regulated the hippocampal and cerebral cortex expressions of NGF and BDNF， and increased the hippocampal number of BrdUlabeled cells. These findings indicate that SFIDPC12CL shows marked antidepressant-like effects in the CMSinduced depression-like model rats， and raise the possibility that SFIDPC12CL up-regulates expressions of NGF and BDNF， and increases neuronal number.
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