Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2024-11-06 DOI:10.1016/j.neuropharm.2024.110209

Yao Huang , Yue You , Wei Wang , Yuan-Hao Chen , Hao Zhang , Qu-Peng Li , Le Liu , Kun Tong , Nan Sun , Jing-Ru Hao , Can Gao

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Abstract

Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.

This article is part of the Special Issue on "Personality Disorders".

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腺苷通过肠道微生物群调节慢性社会挫败应激小鼠的抑郁行为

重度抑郁症（MDD）被认为是全球最普遍的情感障碍。越来越多的元基因组研究表明，肠道微生物群失调在抑郁症的发病中起着至关重要的作用。以前的研究表明，腺苷能缓解肠道菌群失调，这表明提高腺苷水平可能是治疗 MDD 的一种新的干预措施；然而，这种作用的机制仍不清楚。本研究利用16S rRNA基因测序、粪便微生物群移植（FMT）和超高效液相色谱-串联质谱法（UPLC-MS/MS）测试了这样一个假设：增加腺苷含量可通过改变肠道微生物群来缓解遭受慢性社交失败压力（CSDS）的雄性小鼠的抑郁行为。数据显示，易患抑郁症（SUS）的小鼠表现出肠道菌群失调，而来自 SUS 小鼠的 FMT 会增加健康受试者的抑郁样行为。在 SUS 小鼠中，补充腺苷可改善抑郁样行为和肠道微生物群的异常，同时服用益生菌和腺苷不仅可减轻抑郁样行为，还能增强肠道屏障的完整性。通过纳入 83 名抑郁青少年和 67 名健康对照组，该研究发现抑郁组的短链脂肪酸（SCFAs）水平降低了，这一发现与 SUS 小鼠和从 SUS 供体接受 FMT 后的受体小鼠中看到的降低情况相似。相反，补充腺苷或益生菌会增加 SUS 小鼠血清中 SCFAs 的浓度。这些发现表明，腺苷可通过调节肠道微生物群来减轻 CSDS 小鼠的抑郁样行为。这种效果可能与补充腺苷后血清中SCFAs（肠道微生物群产生的代谢产物）的增加有关。

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

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).