Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis.
Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis.
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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。
DOI：
10.3389/fcimb.2017.00489
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发表时间：
2017
影响因子：
5.7
通讯作者：
Xie P
中科院分区：
文献类型：
--
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
肠道微生物是人体内的重要系统，对行为有重要影响。越来越多的研究表明，肠道微生物影响大脑功能和神经发生，包括对压力的敏感性。为了研究微生物定植对行为的影响，我们检测了应激下丘脑-垂体-肾上腺（HPA）轴中与激素和激素受体相关的行为变化。我们测试了无菌（GF）小鼠和无特定病原体（SPF）小鼠，分为四组。采用慢性束缚应激（CRS）方案，在两个应激组中通过将小鼠束缚在锥形离心管中每天4h，持续21天来诱导外部压力。CRS后，GF束缚应激小鼠在OFT的中心和总距离上的探索时间比SPF束缚应激小鼠长。GF束缚应激小鼠HPA轴CRH、ACTH、CORT和ALD水平显著高于SPF束缚应激小鼠。与SPF CRS小鼠相比，GF CRS小鼠Crhr 1 mRNA水平升高。与SPF CRS小鼠相比，GF CRS小鼠的Nr3c2 mRNA水平明显降低。结果表明，在相同的外界应激条件下，SPF小鼠比GF小鼠表现出更多的焦虑样行为。此外，我们还发现GF小鼠与SPF小鼠相比在激素和激素受体方面表现出显着差异。总之，肠道微生物引起的HPA轴失衡可能会影响大脑中的神经内分泌系统，导致焦虑样行为表型。这项研究表明，干预肠道菌群可能为治疗应激相关疾病提供新的途径。
Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA) axis under stress. We tested germ-free (GF) mice and specific pathogen-free (SPF) mice, divided into four groups. A chronic restraint stress (CRS) protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.