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益生菌(植物乳杆菌/双歧双歧杆菌)间歇训练对阿尔茨海默病大鼠被动回避试验、ChAT 和海马 BDNF 的影响。

Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer's disease.

机构信息

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

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

出版信息

Neurosci Lett. 2021 Jun 21;756:135949. doi: 10.1016/j.neulet.2021.135949. Epub 2021 May 8.

Abstract

It has been suggested that gut microbiota dysbiosis can lead to Alzheimer's disease (AD), inducing the production of many AD-related pre-inflammatory cytokines. On the other hand, daily probiotic administration and regular exercise training are assumed to improve clinical AD-related symptoms. To take this line of research further, this study was aimed at investigating the impact of moderate-intensity interval training (MIIT) with a combined administration of Lactobacillus plantarum and Bifidobacterium bifidum (probiotic, BROB) on the passive avoidance test (Shuttle Box), choline acetyltransferase (ChAT) and the brain derived neurotrophic factor (BDNF) in the hippocampus of a rat model of AD. Forty male Wistar rats (280 ± 20 g) were divided into five groups (n = 8 in each) of control, amyloid beta peptide (Aβ), Aβ + MIIT (AD rats undergoing MIIT), Aβ + PROB (AD rats fed Lactobacillus plantarum and Bifidobacterium bifidum), and Aβ + MIIT + PROB (AD rats receiving both treatments). AD was induced by the intra-cerebroventricular injection of Aβ1-42 peptide. MIIT was performed on rodent treadmill for 8 weeks (5 days per week). The probiotic was also fed daily to the related groups for 8 weeks. BDNF and ChAT in the hippocampus were measured by real time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. Cresyl violet staining of brain tissue was performed to evaluate the dead cells. Results of tissue staining showed that the induction of the Alzheimer's led to the destruction of hippocampal cells and induced neurodegeneration (p = 0.001). Results of the shuttle box test showed that short-term memory was improved in the Aβ + MIIT + PROB group compared to the Aβ group, while death cells (dark cells) were decreased in all the other three groups (MIIT, BROB, and Aβ + MIIT + PROB). Levels of ChAT as well as the BDNF mRNA in the Aβ + MIIT + PROB group showed a significant increase compared to the Aβ group. In conclusion, it seems that the use of the combined administration of Lactobacillus plantarum and Bifidobacterium bifidum with interval aerobic exercise can have neuroprotective effects on AD.

摘要

有人提出,肠道微生物群失调可能导致阿尔茨海默病(AD),从而产生许多与 AD 相关的前炎症细胞因子。另一方面,每天服用益生菌和定期进行运动训练被认为可以改善与 AD 相关的临床症状。为了进一步开展这方面的研究,本研究旨在探讨中强度间歇训练(MIIT)联合服用植物乳杆菌和双歧杆菌(益生菌,BROB)对 AD 大鼠模型被动回避测试(穿梭箱)、胆碱乙酰转移酶(ChAT)和脑源性神经营养因子(BDNF)的影响。40 只雄性 Wistar 大鼠(280±20g)分为 5 组(每组 8 只):对照组、淀粉样β肽(Aβ)组、Aβ+MIIT(接受 MIIT 的 AD 大鼠)、Aβ+PROB(给予植物乳杆菌和双歧杆菌的 AD 大鼠)和 Aβ+MIIT+PROB(同时接受两种治疗的 AD 大鼠)。通过向脑室内注射 Aβ1-42 肽诱导 AD。MIIT 在啮齿动物跑步机上进行 8 周(每周 5 天)。相关组也每天给予益生菌。通过实时 PCR(RT-PCR)和免疫组织化学(IHC)分别测量海马体中的 BDNF 和 ChAT。对脑组织进行 Cresyl 紫染色以评估死亡细胞。组织染色结果表明,阿尔茨海默病的诱导导致海马细胞破坏,并诱导神经退行性变(p=0.001)。穿梭箱测试结果表明,与 Aβ 组相比,Aβ+MIIT+PROB 组的短期记忆得到改善,而其他三组(MIIT、BROB 和 Aβ+MIIT+PROB)的死亡细胞(暗细胞)减少。Aβ+MIIT+PROB 组的 ChAT 水平和 BDNF mRNA 水平与 Aβ 组相比均显著增加。总之,似乎联合使用植物乳杆菌和双歧杆菌与间歇有氧运动可以对 AD 产生神经保护作用。

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