Abstract
BackgroundThere are evidences that chlorogenic acid (CGA) has antidepressant effects, however the underlying molecular mechanism has not been well understood. The aim of the study was to explore the neuroprotective effect of CGA on corticosterone (CORT)-induced PC 12 cells and its mechanism, especially the autophagy pathway.MethodsPC12 cells were incubated with CORT (0, 100, 200, 400 or 800 μM) for 24 h, cell viability was measured by MTT assay. PC12 cells were cultured with 400 μM of CORT in the absence or presence of CGA (25 μg/ml) for 24 h, morphologies and specific marker of autophagosome were observed by transmission electron microscope (TEM) and confocal immunofluorescence microscopy, respectively. In addition, PC12 cells were treated with different doses of CGA (0, 6.25, 12.5, 25 or 50 μg/ml) with or without CORT (400 μM) for 24 h, cell viability and changes in the morphology were observed, and further analysis of apoptotic and autophagic proteins, and expression of AKT/mTOR signaling pathway were carried out by Western blot. Specific inhibitors of autophagy 3-Methyladenine (3-MA) and chloroquine (CQ) were added to the PC12 cells cultures to explore the potential role of autophagy in CORT-induced neuronal cell apoptosis.ResultsBesides decreasing PC12 cell activity, CORT could also induce autophagy and apoptosis of PC12 cells, while CGA could reverse these effects. In addition, CGA treatment regulated AKT/mTOR signaling pathway in PC12 cells. CGA, similar to 3-MA and QC, significantly inhibited CORT-induced apoptosis in PC12 cells.ConclusionsOur results provide a new molecular mechanism for the treatment of CORT-induced neurotoxicity by CGA, and suggest CGA may be a potential substance which is can alleviate depression.
Highlights
There are evidences that chlorogenic acid (CGA) has antidepressant effects, the underlying molecular mechanism has not been well understood
Reduction of hippocampal autophagy can ameliorate depression-like behavior in rats [29], and inhibition of neuronal apoptosis regulated by the Protein kinase B (AKT) pathway has neuroprotective effects on chronic unpredictable mild stress (CUMS)-induced depression models [30]
CORT induced autophagy and neurotoxicity in PC12 cells To investigate the induction effect of CORT on autophagy and neurotoxicity of PC12 cells, cells were treated with different concentrations of CORT for 24 h, respectively, and cell viability was determined by MTT assay
Summary
There are evidences that chlorogenic acid (CGA) has antidepressant effects, the underlying molecular mechanism has not been well understood. The aim of the study was to explore the neuroprotective effect of CGA on corticosterone (CORT)-induced PC 12 cells and its mechanism, especially the autophagy pathway. The stress response of the hypothalamic–pituitary–adrenocortical (HPA) axis with a significant rise of glucocorticoid levels has been one of the most thoroughly studied biological systems linked to the pathogenesis of depression [9,10,11,12]. Reduction of hippocampal autophagy can ameliorate depression-like behavior in rats [29], and inhibition of neuronal apoptosis regulated by the AKT pathway has neuroprotective effects on chronic unpredictable mild stress (CUMS)-induced depression models [30]. The biological functions of autophagy and apoptosis in depression are worthy of investigation
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