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益生菌(及NMCC - 14)通过提高单胺水平、多巴胺受体(D1和D2)及突触素的mRNA表达来改善小鼠的应激行为。

Probiotics ( and NMCC-14) Ameliorate Stress Behavior in Mice by Increasing Monoamine Levels and mRNA Expression of Dopamine Receptors (D and D) and Synaptophysin.

作者信息

Rehman Mujeeb Ur, Ghazanfar Shakira, Ul Haq Rizwan, Ullah Shakir, Khan Salman, Wu Jianbo, Ahmad Waqar, Tipu Muhammad Khalid

机构信息

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agricultural Research Centre (NARC), Islamabad, Pakistan.

出版信息

Front Pharmacol. 2022 Jul 19;13:915595. doi: 10.3389/fphar.2022.915595. eCollection 2022.

Abstract

Stress is a physiological consequence of the body to adversity. The gut-brain axis and probiotics are gaining interest to provide better treatment for stress and other neurological disorders. Probiotic ( NMCC-14 and , 10 colony-forming unit/day/animal, per oral) effects were investigated in acute (up to day 7) and subacute (days 8-14) restraint-stressed and normal mice through behavioral paradigms (elevated plus maze: EPM, light dark box/dark light box: LDB, and open field test: OFT). Time spent in the open arms of the EPM, time spent in the light compartment of the LDB, and movable time and time spent in the center of the OFT were significantly ( ≤ 0.05, = 5) increased in probiotic-treated restraint-stressed mice. Enzyme-linked immunoassay determined blood cortisol and adrenocorticotropic hormone (ACTH) levels, which were reduced significantly ( < 0.05, = 5) in probiotic-treated restraint-stressed mice. Hematoxylin and eosin-stained hippocampal slides also showed less or no neurodegeneration in the probiotic-treated animals. High-performance liquid chromatography and quantitative polymerase chain reaction were performed to determine the monoamine levels and mRNA expression of dopamine receptor subtypes (D and D) and synaptophysin in the mice hippocampus (HC) and prefrontal cortex (PFC). The dopamine, serotonin, and norepinephrine levels were also significantly ( < 0.05, = 5) increased in the HC and PFC of probiotic-treated animal brains. Fold expression of mRNA of D and D (except HC, LF-S, day 14) receptors and synaptophysin was also significantly ( < 0.05, = 5) increased in the same brain parts of probiotic-treated restraint-stressed mice. Comparing mice in the NMCC-14 and groups to mice in the normal group, only a significant ( < 0.05, = 5) decrease was observed in the serum ACTH and cortisol levels on day 14 in -treated mice, where all other parameters also showed improvement. In comparison, showed greater stress suppressant activity than NMCC-14. However, both probiotic bacteria can be a better and safer therapeutic alternative for ailments than currently available drugs.

摘要

应激是身体对逆境的一种生理反应。肠-脑轴和益生菌正受到越来越多的关注,有望为应激及其他神经紊乱提供更好的治疗方法。通过行为学范式(高架十字迷宫:EPM、明暗箱/暗明箱:LDB和旷场试验:OFT),研究了益生菌(NMCC-14和,每只动物每天10个菌落形成单位,口服)对急性(至第7天)和亚急性(第8 - 14天)束缚应激小鼠和正常小鼠的影响。在益生菌处理的束缚应激小鼠中,EPM开放臂停留时间、LDB亮区停留时间、旷场试验中的移动时间和中央停留时间均显著增加(P≤0.05,n = 5)。酶联免疫吸附测定法测定血液皮质醇和促肾上腺皮质激素(ACTH)水平,在益生菌处理的束缚应激小鼠中,这些水平显著降低(P<0.05,n = 5)。苏木精和伊红染色的海马切片也显示,益生菌处理的动物中神经退行性变较少或没有。采用高效液相色谱法和定量聚合酶链反应法测定小鼠海马体(HC)和前额叶皮质(PFC)中多巴胺受体亚型(D1和D2)、突触素的单胺水平和mRNA表达。在益生菌处理的动物大脑的HC和PFC中,多巴胺、血清素和去甲肾上腺素水平也显著增加(P<0.05,n = 5)。在益生菌处理的束缚应激小鼠的相同脑区中,D1和D2受体(HC、LF-S组第14天除外)以及突触素的mRNA折叠表达也显著增加(P<0.05,n = 5)。将NMCC-14和组小鼠与正常组小鼠比较,在处理的小鼠中,仅在第14天观察到血清ACTH和皮质醇水平显著降低(P<0.05,n = 5),其他所有参数也显示出改善。相比之下,显示出比NMCC-14更强的应激抑制活性。然而,与目前可用的药物相比,这两种益生菌都可能是治疗疾病的更好、更安全的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bce4/9343877/ad00aa0ca0f2/fphar-13-915595-g001.jpg

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