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干燥综合征小鼠模型中的抑郁样行为:肠道微生物群-脑轴的作用

Depression-like behaviors in mouse model of Sjögren's syndrome: A role of gut-microbiota-brain axis.

作者信息

Pu Yaoyu, He Yangyang, Zhao Xueting, Zhang Qiuping, Wen Ji, Hashimoto Kenji, Liu Yi

机构信息

Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology, Chengdu, China.

出版信息

Pharmacol Biochem Behav. 2022 Sep;219:173448. doi: 10.1016/j.pbb.2022.173448. Epub 2022 Aug 15.

Abstract

Depression is a common psychiatric symptom in patients with Sjögren's syndrome (SS). Prevalence of depression in SS patients is significantly higher than that in the general population. Increasing evidence suggests a crucial role of gut-microbiota-brain axis in depression. In this study, we investigated whether non-obese diabetic (NOD) mice, a widely used animal model of SS, exhibit depression-like phenotypes and abnormal composition of gut microbiota. Eleven-week-old NOD mice spontaneously exhibited SS-related symptoms without pancreatic destruction. NOD mice displayed depression-like behaviors, decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Interestingly, SS-related proinflammatory factors in the submandibular gland (SMG) and autoantibodies (anti-SSA and anti-SSB) in the plasma were correlated with the expression of synaptic proteins in the PFC or depression-like behaviors. In addition, there were correlations between the relative abundance of microbiota and SS-related symptoms (or depression-related phenotypes). These data suggest that SS-related symptoms and abnormal composition of gut microbiota may play a role in depression-like phenotypes in NOD mice through gut-microbiota-brain axis.

摘要

抑郁症是干燥综合征(SS)患者常见的精神症状。SS患者中抑郁症的患病率显著高于普通人群。越来越多的证据表明肠道微生物群-脑轴在抑郁症中起关键作用。在本研究中,我们调查了广泛使用的SS动物模型非肥胖糖尿病(NOD)小鼠是否表现出抑郁样表型和肠道微生物群组成异常。11周龄的NOD小鼠在没有胰腺破坏的情况下自发出现SS相关症状。NOD小鼠表现出抑郁样行为、前额叶皮质(PFC)中突触蛋白表达降低以及肠道微生物群组成异常。有趣的是,下颌下腺(SMG)中与SS相关的促炎因子和血浆中的自身抗体(抗SSA和抗SSB)与PFC中突触蛋白的表达或抑郁样行为相关。此外,微生物群的相对丰度与SS相关症状(或抑郁相关表型)之间存在相关性。这些数据表明,SS相关症状和肠道微生物群组成异常可能通过肠道微生物群-脑轴在NOD小鼠的抑郁样表型中起作用。

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