INTRODUCTION Inflammation and oxidative/nitrative stress induced by chronic psychosocial or physical stress play fundamental roles in the pathogenesis of depression, and lead to the loss of neurotrophic support, decreased neurogenesis and synaptic plasticity in the hippocampus. Findings have shown inhibition of inflammation waterfall may offer new approaches to the treatment of depression, especially for patients with treatment-resistant depression (TRD). Cerium Oxide (CeO2) is the oxide form of cerium, a rare earth element in the lanthanide series. Cerium oxide nanoparticles (CeO2NPs) are potent regenerative antioxidant and anti-inflammatory agents. We evaluated the neuroprotective and the neuronal plasticity activities of CeO2NPs in the stress-induced model of depression. METHODS We have analyzed the effects of single-dose intrahippocampal and intracerebroventricular (ICV) injections of CeO2NPs treatment on immobility behavior (forced swimming test), hippocampal IL-6 and malondialdehyde (Elisa), cell survival (Nissl staining), dentate gyrus BrdU-positive cells (Immunohistofluorescence) and growth associated protein-43 (GAp-43) expression (Immunohistofluorescence) of the hippocampal CA3 region. RESULTS In our study, single-dose CeO2NPs treatment could effectively suppress inflammatory and oxidative markers level induced by unpredictable chronic mild stress (UCMS) and improved immobility behavior, increased hippocampal cell proliferation, cell survival and neurite outgrowth, and thereby, prevented the progression of hippocampal destruction and dysfunction. CONCLUSION This study demonstrates a new prospect for the treatment of depression. Our study gives us the confidence to continue the investigation of CeO2 NPs as a novel therapy, especially, for TRD that characterized by chronic and persistent inflammation.

中文翻译：

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氧化铈纳米颗粒对雄性大鼠实验性应激性抑郁症的神经保护作用

引言 慢性社会心理或身体压力引起的炎症和氧化/硝化应激在抑郁症的发病机制中起重要作用，并导致海马神经营养支持的丧失、神经发生和突触可塑性降低。研究结果表明，抑制炎症瀑布可能为治疗抑郁症提供新的方法，尤其是对于难治性抑郁症 (TRD) 患者。氧化铈 (CeO2) 是铈的氧化物形式，铈是镧系元素中的一种稀土元素。氧化铈纳米颗粒 (CeO2NPs) 是有效的再生抗氧化剂和抗炎剂。我们评估了压力诱导的抑郁模型中 CeO2NPs 的神经保护和神经元可塑性活动。方法我们分析了单剂量海马内和脑室内 (ICV) 注射 CeO2NPs 治疗对不动行为（强迫游泳试验）、海马 IL-6 和丙二醛（Elisa）、细胞存活（尼氏染色）、齿状回 BrdU-海马 CA3 区域的阳性细胞（免疫组织荧光）和生长相关蛋白 43（GAp-43）表达（免疫组织荧光）。结果在我们的研究中，单剂量 CeO2NPs 治疗可以有效抑制不可预测的慢性轻度应激 (UCMS) 诱导的炎症和氧化标志物水平并改善不动行为，增加海马细胞增殖、细胞存活和神经突生长，从而防止进展海马体破坏和功能障碍。结论 本研究为抑郁症的治疗开辟了新的前景。我们的研究使我们有信心继续将 CeO2 NPs 作为一种新疗法进行研究，特别是对于以慢性和持续炎症为特征的 TRD。