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鼠慢性不可预测轻度应激模型中,补充鼠李糖乳杆菌 JB-1 可恢复大脑神经化学平衡并缓解情绪障碍进展。

Dietary supplementation with Lactobacillus rhamnosus JB-1 restores brain neurochemical balance and mitigates the progression of mood disorder in a rat model of chronic unpredictable mild stress.

机构信息

Department of Radiography, Medical University of Lublin, Lublin, Poland.

Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.

出版信息

Nutr Res. 2020 Oct;82:44-57. doi: 10.1016/j.nutres.2020.06.019. Epub 2020 Jul 6.

Abstract

Major depressive disorder is a stress-related disease associated with brain metabolic dysregulation in the glutamine-glutamate/γ-aminobutyric acid (Gln-Glu/GABA) cycle. Recent studies have demonstrated that microbiome-gut-brain interactions have the potential to influence mental health. The hypothesis of this study was that Lactobacillus rhamnosus JB-1 (LR-JB1™) dietary supplementation has a positive impact on neuro-metabolism which can be quantified in vivo using magnetic resonance spectroscopy (MRS). A rat model of depressive-like disorder, chronic unpredictable mild stress (CUMS), was used. Baseline comparisons of MRS and behavior were obtained in a control group and in a stressed group subjected to CUMS. Of the 22 metabolites measured using MRS, stressed rats had significantly lower concentrations of GABA, glutamate, glutamine + glutathione, glutamate + glutamine, total creatine, and total N-acetylaspartate (tNAA). Stressed rats were then separated into 2 groups and supplemented with either LR-JB1™ or placebo and re-evaluated after 4 weeks of continued CUMS. The LR-JB1™ microbiotic diet restored these metabolites to levels previously observed in controls, while the placebo diet resulted in further significant decrease of glutamate, total choline, and tNAA. LR-JB1™ treated animals also exhibited calmer and more relaxed behavior, as compared with placebo treated animals. In summary, significant cerebral biochemical downregulation of major brain metabolites following prolonged stress were measured in vivo using MRS, and these decreases were reversed using a microbiotic dietary supplement of LR-JB1™, even in the presence of continued stress, which also resulted in a reduction of stress-induced behavior in a rat model of depressive-like disorder.

摘要

重度抑郁症是一种与谷氨酰胺-谷氨酸/γ-氨基丁酸(Gln-Glu/GABA)循环中的脑代谢失调有关的应激相关疾病。最近的研究表明,微生物组-肠道-大脑相互作用有可能影响心理健康。本研究的假设是,鼠李糖乳杆菌 JB-1(LR-JB1™)饮食补充对神经代谢有积极影响,这可以使用磁共振波谱(MRS)在体内进行量化。使用慢性不可预测轻度应激(CUMS)建立了一种类似于抑郁症的大鼠模型。在对照组和接受 CUMS 的应激组中获得了 MRS 和行为的基线比较。在使用 MRS 测量的 22 种代谢物中,应激大鼠的 GABA、谷氨酸、谷氨酰胺+谷胱甘肽、谷氨酸+谷氨酰胺、总肌酸和总 N-乙酰天冬氨酸(tNAA)浓度显著降低。然后,将应激大鼠分为 2 组,分别用 LR-JB1™或安慰剂补充,并在继续接受 CUMS 4 周后重新评估。LR-JB1™微生物饮食将这些代谢物恢复到以前在对照组中观察到的水平,而安慰剂饮食导致谷氨酸、总胆碱和 tNAA 进一步显著降低。与安慰剂治疗的动物相比,LR-JB1™ 治疗的动物还表现出更平静和放松的行为。总之,使用 MRS 在体内测量了长时间应激后主要大脑代谢物的显著大脑生化下调,并且使用 LR-JB1™的微生物饮食补充剂逆转了这些下调,即使在持续应激的情况下也是如此,这也导致了抑郁样障碍大鼠模型中应激诱导行为的减少。

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