Neuropathological implication of high blood bilirubin in patients and model rats with depression

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Yejun Gao , Yian Ling , Jing Li , Yayun Xu , Jinfang Ge , Qingrong Xia
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引用次数: 0

Abstract

Purpose

Elevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior.

Patients and methods

Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively.

Results

Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress.

Conclusion

Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.

抑郁症患者和模型大鼠高血胆红素对神经病理学的影响。
目的:胆红素水平升高与重度抑郁障碍(MDD)有关;然而,胆红素对MDD的确切影响及其潜在的分子机制仍不清楚。在此,我们探讨了胆红素对MDD的影响,并试图确定胆红素诱发抑郁样行为的机制:纳入 40 名被诊断为 MDD 并接受选择性血清素再摄取抑制剂(SSRIs)治疗的患者,43 名健康志愿者作为对照。临床症状采用汉密尔顿抑郁评分量表-24(HAMD-24)和汉密尔顿焦虑评分量表进行评估。使用自动生化分析仪测量基线和治疗后的血清总胆红素(TBIL)和间接胆红素(IBIL)浓度。临床症状与总胆红素或间接胆红素之间的关系采用皮尔逊相关性进行检验。采用慢性束缚应激(CRS)生成大鼠抑郁模型。大鼠血清中的 TBIL 和 IBIL 用 ELISA 法测定。大鼠海马组织中的活性氧(ROS)含量通过流式细胞术进行量化。免疫荧光和透射电子显微镜分别评估了大鼠海马的小胶质细胞标记物水平和神经元损伤程度:结果:多发性硬化症患者的血清TBIL和IBIL水平高于健康对照组。使用 SSRIs 治疗后,MDD 患者血清中的 TBIL 和 IBIL 水平明显降低。MDD 患者的 TBIL 和 IBIL 水平与 HAMD-24 相关。与对照组相比,CRS 暴露大鼠血清中 TBIL、IBIL 水平和海马 ROS 含量升高。氟西汀可降低炎症因子水平,减轻氧化应激:我们的研究结果表明,血清胆红素升高与抑郁症状之间可能存在关联。ROS水平的升高以及神经元损伤可能代表了多发性抑郁症的病理机制。
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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来源期刊
Brain Research Bulletin
Brain Research Bulletin 医学-神经科学
CiteScore
6.90
自引率
2.60%
发文量
253
审稿时长
67 days
期刊介绍: The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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