Departments of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China.
Departments of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China.
J Affect Disord. 2022 Dec 1;318:152-158. doi: 10.1016/j.jad.2022.08.059. Epub 2022 Sep 6.
Intestinal dysbacteriosis is associated with depression. This study aimed to establish an antibiotics-induced depression mouse model and explore the mechanism of antibiotic-induced depression.
C57BL/6 J mice were treated with antibiotics to prepare the antibiotic-induced depression mouse model. Behavioral tests and depression-related bio-markers were examined. To understand the abundance of different bacteria in intestinal flora and screen out the predominant bacterial species, metagenomic analysis of feces was carried out. Finally, we detected the expression of NF-κB-p65 and p-NF-κB-p65 in PFC and the hippocampus using Western blot.
Mixtures A and B caused depression-like behavior in mice. Norepinephrine, 5-hydroxytryptamine, and brain-derived neurotrophic factor in hippocampus and PFC of antibiotic-induced depression mice significantly decreased. The serum adrenocorticotropic hormone and corticosterone concentrations increased. The abundance values of Bacteroides thetaiotaomicron, Klebsiella oxytoca, and Klebsiella aerogenes in antibiotic-induced depression mice significantly increased, and the characteristic KO genes and metabolic pathways in antibiotic-induced depression mice were significantly different with in CUMS depression mice (the positive control) and normal mice. The relative levels of p-NF-κB-p65 in antibiotics-induced depression mice were significantly higher than in normal mice.
How dysbacteriosis induces inflammation in the central nervous system is unclear.
Specific antibiotic mixture can cause depression-like behavior and changes of depression-related bio-markers in mice. The antibiotic-induced depression mice display changes in the species and metabolism of intestinal bacterial flora. The activation of NF-κB inflammatory signaling pathway in the central nervous system may act as one of the mechanisms in the development of antibiotic-induced depression.
肠道菌群失调与抑郁症有关。本研究旨在建立抗生素诱导的抑郁小鼠模型，探讨抗生素诱导抑郁的机制。
采用抗生素处理 C57BL/6J 小鼠制备抗生素诱导的抑郁小鼠模型。检测行为学及与抑郁相关的生物标志物。通过宏基因组分析粪便，了解肠道菌群中不同细菌的丰度，筛选出优势菌属。最后，采用 Western blot 检测前额叶皮质和海马中 NF-κB-p65 和 p-NF-κB-p65 的表达。
混合 A 和 B 可引起小鼠出现抑郁样行为。抗生素诱导的抑郁小鼠海马和前额叶皮质中的去甲肾上腺素、5-羟色胺和脑源性神经营养因子显著降低，血清促肾上腺皮质激素和皮质酮浓度升高。抗生素诱导的抑郁小鼠中拟杆菌属、产酸克雷伯菌和产气克雷伯菌的丰度值显著增加，且抗生素诱导的抑郁小鼠的特征 KO 基因和代谢途径与慢性不可预知温和应激抑郁小鼠（阳性对照）和正常小鼠均显著不同。抗生素诱导的抑郁小鼠中 p-NF-κB-p65 的相对水平明显高于正常小鼠。
肠道菌群失调如何引起中枢神经系统炎症尚不清楚。
特定的抗生素混合物可引起小鼠出现抑郁样行为及抑郁相关生物标志物的改变。抗生素诱导的抑郁小鼠表现出肠道菌群物种和代谢的变化。中枢神经系统中 NF-κB 炎症信号通路的激活可能是抗生素诱导抑郁发生的机制之一。
