Stanniocalcin-1 Overexpression Prevents Depression-Like Behaviors Through Inhibition of the ROS/NF-κB Signaling Pathway

Bin Chao,Lili Zhang,Yuxia Chen,Juhua Pan,Ying Zhang,Manman Xu,Shijing Huang

doi:10.3389/fpsyt.2021.644383

Bin Chao, Lili Zhang + Show 5 more

Open Access

https://doi.org/10.3389/fpsyt.2021.644383

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Abstract

Background: Depression is a burdensome psychiatric disorder presenting with disordered inflammation and neural plasticity. We conducted this study with an aim to explore the effect of stanniocalcin-1 (STC1) on inflammation and neuron injury in rats with depression-like behaviors.Methods: A model of depression-like behaviors was established in Wistar rats by stress stimulation. Adeno-associated virus (AAV)-packaged STC1 overexpression sequence or siRNA against STC1 was introduced into rats to enhance or silence the STC1 expression. Moreover, we measured pro-inflammatory and anti-inflammatory proteins, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and reactive oxygen species (ROS) production. An in vitro model was induced in hippocampal neurons by CORT to explore the effect of STC1 on the neuron viability, toxicity and apoptosis. RT-qPCR and Western blot assay were employed to determine the expression of STC1 and nuclear factor κB (NF-κB) signaling pathway-related genes.Results: STC1 was under-expressed in the hippocampus of rats with depression-like behaviors, while its overexpression could reduce the depression-like behaviors in the stress-stimulated rats. Furthermore, overexpression of STC1 resulted in enhanced neural plasticity, reduced release of pro-inflammatory proteins, elevated SOD and CAT and diminished MDA level in the hippocampus of rats with depression-like behaviors. Overexpressed STC1 blocked the ROS/NF-κB signaling pathway, thereby enhancing the viability of CORT-treated neurons while repressing their toxicity and apoptosis.Conclusion: Collectively, overexpression of STC1 inhibits inflammation and protects neuron injury in rats with depression-like behaviors by inactivating the ROS/NF-κB signaling pathway.

Highlights

Depression is regarded as a disabling chronic mental disease (1), and afflicts ∼300 million individuals on a global scale (2)
Overexpression of STC1 resulted in enhanced neural plasticity, reduced release of pro-inflammatory proteins, elevated superoxide dismutase (SOD) and CAT and diminished MDA level in the hippocampus of rats with depression-like behaviors
The rats were exposed to stimulation of chronic unpredictable mild stress for 5 weeks, during which the rats were deprived of food and water for 24 h, respectively, and subjected to 45◦ cage tilt for 24 h, 5-min cold-water swimming at 4 ◦C, wet bedding for 24 h, foot electric shock at 0.5 mA for 0.5 s, physical restraint for 2 h, cage shaking for 2 h, and overnight illumination

Summary

Introduction

Depression is regarded as a disabling chronic mental disease (1), and afflicts ∼300 million individuals on a global scale (2). Depression is prone to cause a huge burden to the patients by diminishing their life quality and threatening their somatic health; it has been revealed to elevate the risk of other diseases such as stroke and diabetes (6). Antidepressants are recommended as the standard treatment for adult patients suffering from moderate to severe major depression, but the efficacy is still not satisfactory in some individuals (7). Against such backdrop, it is still important to seek novel target for treatment of depression. Depression is a burdensome psychiatric disorder presenting with disordered inflammation and neural plasticity. We conducted this study with an aim to explore the effect of stanniocalcin-1 (STC1) on inflammation and neuron injury in rats with depression-like behaviors

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Results

Conclusion