Table_1_Stanniocalcin-1 Overexpression Prevents Depression-Like Behaviors Through Inhibition of the ROS/NF-κB Signaling Pathway.DOCX

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.

研究背景：抑郁症是一种负担沉重的精神疾病，伴随炎症紊乱与神经可塑性异常。本研究旨在探讨司他钙素-1（stanniocalcin-1, STC1）对抑郁样行为大鼠炎症反应与神经元损伤的影响。
研究方法：通过应激刺激构建Wistar大鼠抑郁样行为模型。将包装有腺相关病毒（adeno-associated virus, AAV）的STC1过表达序列或靶向STC1的小干扰RNA（small interfering RNA, siRNA）导入大鼠体内，以上调或沉默STC1的表达。此外，本研究检测了促炎与抗炎蛋白、超氧化物歧化酶（superoxide dismutase, SOD）、过氧化氢酶（catalase, CAT）、丙二醛（malondialdehyde, MDA）水平及活性氧（reactive oxygen species, ROS）生成量。采用皮质酮（CORT）处理海马神经元构建体外模型，以探究STC1对神经元活力、细胞毒性及细胞凋亡的影响。通过逆转录实时定量聚合酶链反应（reverse transcription quantitative polymerase chain reaction, RT-qPCR）与蛋白质印迹（Western blot）实验，检测STC1及核因子κB（nuclear factor κB, NF-κB）信号通路相关基因的表达水平。
研究结果：抑郁样行为大鼠海马组织中STC1呈低表达，而过表达STC1可减轻应激刺激大鼠的抑郁样行为。进一步研究发现，在抑郁样行为大鼠的海马组织中，STC1过表达可提升神经可塑性，减少促炎蛋白释放，提高SOD与CAT活性，并降低MDA水平。STC1过表达可阻断ROS/NF-κB信号通路，进而提高CORT处理的海马神经元活力，同时抑制其细胞毒性与凋亡。
研究结论：综上，STC1过表达可通过失活ROS/NF-κB信号通路，抑制抑郁样行为大鼠的炎症反应并减轻神经元损伤。