Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.
Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.
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肠道微生物群通过海马体中的糖皮质激素受体途径基因调节小鼠行为。
DOI：
10.1038/s41398-018-0240-5
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发表时间：
2018-09-07
影响因子：
6.8
通讯作者：
Xie P
中科院分区：
文献类型：
--
作者：
Luo Y;Zeng B;Zeng L;Du X;Li B;Huo R;Liu L;Wang H;Dong M;Pan J;Zheng P;Zhou C;Wei H;Xie P
肠道菌群在免疫系统、代谢、消化等方面具有重要作用，对神经系统也有重要影响。近年来的研究表明，肠道菌群异常可诱发异常行为，这可能与下丘脑-垂体-肾上腺（HPA）轴有关。因此，我们通过行为测试研究无菌（GF）小鼠的行为变化，定量血清基础皮质醇水平，并通过微阵列分析和实时PCR验证检测海马糖皮质激素受体通路基因，探索肠道微生物群影响宿主行为和脑功能的分子机制。此外，我们在大肠杆菌衍生的脂多糖（LPS）治疗小鼠模型和粪便“抑郁微生物群”移植小鼠模型中量化了基础血清皮质醇水平，并通过实时荧光定量PCR验证了差异基因。我们发现GF小鼠表现出抗焦虑和抗抑郁样行为，而大肠杆菌lps处理的小鼠表现出抗抑郁样行为，但没有表现出抗焦虑样行为。然而，“抑郁微生物群”受体小鼠表现出焦虑和抑郁样行为。此外，6个糖皮质激素受体通路基因（Slc22a5、Aqp1、Stat5a、Ampd3、Plekhf1和Cyb561）在GF小鼠中上调，其中只有两个基因（Stat5a和Ampd3）在lps处理小鼠中上调，而共享基因Stat5a在“抑郁微生物群”受体小鼠中下调。此外，大肠杆菌lps处理小鼠的基础血清皮质醇水平降低，而GF小鼠和“抑郁微生物群”受体小鼠则没有。这些结果表明，肠道微生物群可能通过糖皮质激素受体的下游途径导致小鼠行为异常。在此，我们提出了肠道微生物群影响抑郁样行为的分子机制的新见解。
Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic–pituitary–adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host’s behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal “depression microbiota” transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, “depression microbiota” recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in “depression microbiota” recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and “depression microbiota” recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.
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影响因子：
4.1
作者：
Furigo, Isadora C.;Ramos-Lobo, Angela M.;Donato, J., Jr.
通讯作者：
Donato, J., Jr.
DOI：
10.1080/10408398.2013.876960
发表时间：
2016-11-17
影响因子：
10.2
作者：
Du J;Zhu M;Bao H;Li B;Dong Y;Xiao C;Zhang GY;Henter I;Rudorfer M;Vitiello B
通讯作者：
Vitiello B
影响因子：
2.7
作者：
Byrne G;Rosenfeld G;Leung Y;Qian H;Raudzus J;Nunez C;Bressler B
通讯作者：
Bressler B
微生物群调节下丘脑-垂体-肾上腺轴的焦虑样行为和内分泌异常。
影响因子：
5.7
作者：
Huo R;Zeng B;Zeng L;Cheng K;Li B;Luo Y;Wang H;Zhou C;Fang L;Li W;Niu R;Wei H;Xie P
通讯作者：
Xie P
影响因子：
3.4
作者：
Cenacchi, Lucia;Busch, Manuela;Lancaster, C. Roy D.
通讯作者：
Lancaster, C. Roy D.