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双歧杆菌和植物乳杆菌联合运动训练 8 周可减轻阿尔茨海默病大鼠模型中 Aβ 的神经毒性及乙酰胆碱介导的空间学习障碍。

An 8-Week Administration of Bifidobacterium bifidum and Lactobacillus plantarum Combined with Exercise Training Alleviates Neurotoxicity of Aβ and Spatial Learning via Acetylcholine in Alzheimer Rat Model.

机构信息

Department of Physical Education and Sport Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.

出版信息

J Mol Neurosci. 2021 Jul;71(7):1495-1505. doi: 10.1007/s12031-021-01812-y. Epub 2021 Mar 14.

DOI:10.1007/s12031-021-01812-y
PMID:33715084
Abstract

This study aimed to determine the effects of 8 weeks of an administration of Bifidobacterium bifidum and Lactobacillus plantarum combined with exercise training on neurotoxicity of Aβ, spatial learning, acetylcholine (ACH), and vascular endothelial growth factor (VEGF) in Alzheimer rats. Twenty-five Wistar rats were randomly divided into 5 groups (n = 5 in each): (1) healthy control (control), (2) Alzheimer disease (AD), (3) AD with treadmill exercise (AD + Exe), (4) AD with probiotic (combined administration of Bifidobacterium bifidum and Lactobacillus plantarum) treatment (AD + Pro), and (5) AD with treadmill exercise and probiotic treatment (AD + Exe + Pro). AD was induced by intra-cerebroventricular injection of Aβ1-42 peptide. Then, the training groups exercised on treadmill for 8 weeks, 5 days per weeks. The rats were treated daily with probiotic supplements via gavage for 8 weeks. The Morris water maze (MWM) test was administered to measure spatial learning. Then, the animals were sacrificed and Vegf and ACH were analyzed using the qPCR and immunohistochemistry (IHC) methods, respectively. Results showed that the β-amyloid plaques were significantly increased in the brains of the AD group compared with the control group (p < 0.001). The combined use of probiotics and exercise training significantly increased the time spent in the target quadrant after removing the platform, compared with the AD group in the Morris water maze test (p < 0.001). Crystal violet analysis showed that sole (p < 0.01) and combined exercise training and probiotic supplementation (p < 0.001) significantly reduced the number of dead cells in the brains of rats compared with the AD group. AD significantly decreased Vegf mRNA and ACH in the CA1 area of the hippocampus (p < 0.001). However, mono and combined therapy (exercise and probiotics) significantly increased ACH in the rats' brain compared with the AD group. Overall, 8 weeks of an administration of Bifidobacterium bifidum and Lactobacillus plantarum combined with exercise training can improve spatial learning impairment in the AD rats. Exercise and probiotics seem to offer potential benefits to AD patients by upregulating ACH.

摘要

这项研究旨在确定双歧杆菌和植物乳杆菌联合运动训练 8 周对阿尔茨海默病大鼠神经毒性、空间学习、乙酰胆碱(ACH)和血管内皮生长因子(VEGF)的影响。25 只 Wistar 大鼠随机分为 5 组(每组 5 只):(1)健康对照组(对照组)、(2)阿尔茨海默病组(AD 组)、(3)AD 与跑步机运动组(AD+Exe 组)、(4)AD 与益生菌治疗组(双歧杆菌和植物乳杆菌联合治疗)(AD+Pro 组)和(5)AD 与跑步机运动和益生菌治疗组(AD+Exe+Pro 组)。AD 通过脑室内注射 Aβ1-42 肽诱导。然后,训练组每周 5 天进行 8 周跑步机运动。大鼠每日通过灌胃给予益生菌补充剂进行 8 周治疗。使用 Morris 水迷宫(MWM)测试测量空间学习。然后,处死动物,使用 qPCR 和免疫组织化学(IHC)方法分别分析 Vegf 和 ACH。结果表明,与对照组相比,AD 组大脑中的β-淀粉样斑块明显增加(p<0.001)。在 Morris 水迷宫测试中,与 AD 组相比,益生菌和运动训练的联合使用显著增加了移除平台后在目标象限花费的时间(p<0.001)。结晶紫分析表明,单独(p<0.01)和联合运动训练和益生菌补充(p<0.001)显著减少了 AD 组大鼠大脑中死亡细胞的数量。AD 显著降低了海马 CA1 区 Vegf mRNA 和 ACH(p<0.001)。然而,单独和联合治疗(运动和益生菌)显著增加了大鼠大脑中的 ACH。总体而言,双歧杆菌和植物乳杆菌联合运动训练 8 周可改善 AD 大鼠的空间学习障碍。运动和益生菌似乎通过上调 ACH 为 AD 患者提供了潜在的益处。

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