Depression-like Behavior Induced by Repeated Administration of Dexamethasone to Lipopolysaccharide-inflamed Mice.

Fumiya Shibagaki, Naoko Kojima, Akane Furukawa, Noritaka Nakamichi
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Abstract

Background: Over the years, animal models of depression have been developed by loading chronic stress, inducing neuroinflammation, or administering drugs that induce depression; however, these results have poor reproducibility. Therefore, it is necessary to develop animal models that exhibit definitive symptoms of depression for studies on potential therapeutics.

Objective: This study was aimed at investigating depression-like symptoms and their pathogenesis in lipopolysaccharide (LPS)-inflamed mice treated with dexamethasone (DEX).

Methods: Male ICR mice were injected with LPS, followed by injection with DEX a day later and each day for 6 consecutive days. Depression-like behavior, expression of the glial markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1), and the number of the immature neuronal marker doublecortin (DCX)-positive cells were assessed using tail-suspension test (TST), forced swim test (FST), western blot analysis, and immunohistochemical analysis.

Results: Mice in the LPS+DEX group had significantly longer immobility time in the TST and FST than did those in the LPS- or DEX-only and control groups on day 7 post-LPS administration. GFAP and Iba1 expression was significantly elevated in the hippocampus of mice in the LPS group than in those of mice in the control group. Moreover, a significantly lower number of DCX-positive cells was observed in the hippocampal dentate gyrus of mice in the LPS+DEX group compared with that in mice in the LPS- or DEX-only and control groups on day 7 after LPS administration.

Conclusion: Repeated DEX administration to LPS-inflamed mice may induce definitive depression-like symptoms by decreasing the number of immature neurons in the hippocampal dentate gyrus. This novel mouse model of depression was produced by repeated administration of steroids to inflamed mice.

反复给发炎的脂多糖小鼠注射地塞米松诱发抑郁样行为
背景:多年来,人们通过加载慢性应激、诱发神经炎症或服用诱发抑郁症的药物等方法建立了抑郁症动物模型;然而,这些结果的可重复性很差。因此,有必要开发能表现出抑郁症明确症状的动物模型,以研究潜在的治疗方法:本研究旨在探讨用地塞米松(DEX)治疗脂多糖(LPS)炎症小鼠的抑郁症状及其发病机制:方法:给雄性ICR小鼠注射LPS,一天后注射DEX,连续6天每天注射。采用尾悬吊试验(TST)、强迫游泳试验(FST)、Western印迹分析和免疫组化分析评估抑郁样行为、胶质标记物胶质纤维酸性蛋白(GFAP)和电离钙结合适配器分子1(Iba1)的表达以及未成熟神经元标记物双皮质素(DCX)阳性细胞的数量:结果:在注射 LPS 后第 7 天,LPS+DEX 组小鼠在 TST 和 FST 中的静止时间明显长于仅注射 LPS 或 DEX 组和对照组小鼠。LPS 组小鼠海马的 GFAP 和 Iba1 表达明显高于对照组。此外,在注射 LPS 后第 7 天,在 LPS+DEX 组小鼠的海马齿状回中观察到的 DCX 阳性细胞数量明显少于注射 LPS 或仅注射 DEX 组和对照组的小鼠:结论:对LPS炎症小鼠重复给予DEX可通过减少海马齿状回中未成熟神经元的数量诱发明确的抑郁症状。这种新型抑郁症小鼠模型是通过对发炎小鼠重复施用类固醇而产生的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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