Abstract
Purpose: To investigate the effect and mechanism of curcumin on depression in mice
 Methods: Mice were subjected to chronic unpredictable mild stress (CUMS), and behavioural changes were evaluated by sucrose preference test (SPT) and forced swimming test (FST). CUMS-treated mice received curcumin at a concentration of 50, 100, or 200 mg/kg. The level of MiR-124 was measured by real-time polymerase chain reaction (RT-PCR). Brain-derived neurotrophic factor (BDNF) levels were evaluated by western blotting.
 Results: CUMS induced depressive behaviour in mice, with increase in miR-124 and decrease in BDNF. Curcumin inhibited miR-124 expression and promoted BDNF in a dose-dependent manner in CUMS-treated mice. Brain-derived neurotrophic factor was the direct target of miR-124, decreasing the transcription of BDNF, but this was reversed by curcumin in vitro. MicroRNA-124 overexpression aggravated CUMS-induced depressive symptoms including loss of appetite, less sucrose consumption, shorter swimming time, and longer immobility time (p < 0.001). The effects were attenuated by curcumin.
 Conclusion: Curcumin alleviates CUMS-induced depressive behaviour by regulating miR-124/BDNF, suggesting that curcumin may a viable treatment option for depression.
Highlights
Depression is a common psychiatric disorder characterised by emotional or physical problems such as low mood, loss of memory, hopelessness, and insomnia [1]
chronic unpredictable mild stress (CUMS)-treated mice were treated with different concentrations of curcumin (0, 50, 100, 200 mg/kg)
The transfection efficiency of miR-124 mimics were analysed by real-time polymerase chain reaction (RT-PCR), and the results indicated that the miR-124 level was increased in transfected 293T cells when compared with control
Summary
Depression is a common psychiatric disorder characterised by emotional or physical problems such as low mood, loss of memory, hopelessness, and insomnia [1]. MiRNAs are 20 to 25-nucleotide long non-coding regulatory RNAs that affect diverse biological processes by regulating mRNA translation or gene expression [4]. MiRNAs are abundant in the brain and play vital roles in many physiological processes[5]. Many studies have reported that miRNA dysregulation affects depression course in patients with major depressive disorder (MDD) patients, as well as in animal models [6,7]. MiR-124 is abundant in the mouse brain [8]. MiR-124 levels in peripheral blood mononuclear cells (PBMCs) in MDD patients were significantly higher than in healthy people. The level of miR124 in patients decreased markedly [9], which suggesting that miR-124 plays a vital function in the process of MDD
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