Research Centre for Molecular Exercise Science, Hungarian University of Sport Science, Alkotas str. 44, Budapest, 1123, Hungary.
Sports Neuroscience Division, Advanced Research Initiative for Human High Performance (ARIHHP), Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8574, Japan.
BMC Neurosci. 2023 Dec 18;24(1):68. doi: 10.1186/s12868-023-00836-x.
It has been suggested that exercise training and postbiotic supplement could decelerate the progress of functional and biochemical deterioration in double transgenic mice overexpresses mutated forms of the genes for human amyloid precursor protein (APP) and presenilin 1 (m146L) (APP/PS1). Our earlier published data indicated that the mice performed better than controls on the Morris Maze Test parallel with decreased occurrence of amyloid-β plaques in the hippocampus. We investigated the neuroprotective and therapeutic effects of high-intensity training and postbiotic supplementation.
Thirty-two adult APP/PS1 mice were randomly divided into four groups: (1) control, (2) high-intensity training (3) postbiotic, (4) combined (training and postbiotic) treatment for 20 weeks. In this study, the whole hemibrain without hippocampus was used to find molecular traits explaining improved brain function. We applied qualitative RT-PCR for gene expression, Western blot for protein level, and Zymography for LONP1 activity. Disaggregation analysis of Aβ-40 was performed in the presence of Lactobacillus acidophilus and Bifidobacterium longum lysate.
We found that exercise training decreased Alzheimer's Disease (AD)-related gene expression (NF-kB) that was not affected by postbiotic treatment. The preparation used for postbiotic treatment is composed of tyndallized Bifidobacterium longum and Lactobacillus acidophilus. Both of the postbiotics effectively disaggregated amyloid-β/Aβ-40 aggregates by chelating Zn and Cu ions. The postbiotic treatment decreased endogenous human APP protein expression and mouse APP gene expression in the hemibrains. In addition, the postbiotic treatment elevated mitochondrial LONP1 activity as well.
Our findings revealed distinct mechanisms behind improved memory performance in the whole brain: while exercise training modulates NF-kB signaling pathway regulating immune response until postbiotic diminishes APP gene expression, disaggregates pre-existing amyloid-β plaques and activates mitochondrial protein quality control in the region of brain out of hippocampus. Using the above treatments complements and efficiently slows down the development of AD.
有人提出，运动训练和后生元补充可以减缓过度表达人类淀粉样前体蛋白（APP）和早老素 1（m146L）（APP/PS1）基因突变的双转基因小鼠的功能和生化恶化进程。我们之前发表的数据表明，与对照组相比，这些小鼠在 Morris 水迷宫测试中表现更好，同时海马体中淀粉样-β斑块的发生率降低。我们研究了高强度训练和后生元补充的神经保护和治疗作用。
32 只成年 APP/PS1 小鼠被随机分为四组：（1）对照组，（2）高强度训练组，（3）后生元组，（4）联合（训练和后生元）治疗组，共 20 周。在这项研究中，使用不包含海马体的整个半脑来寻找解释改善大脑功能的分子特征。我们应用定性 RT-PCR 进行基因表达、Western blot 进行蛋白水平和 Zymography 进行 LONP1 活性检测。在乳酸杆菌和双歧杆菌裂解物的存在下，对 Aβ-40 进行解聚分析。
我们发现运动训练降低了阿尔茨海默病（AD）相关基因表达（NF-kB），而后生元处理没有影响。后生元处理使用的制剂由经过 Tyndallization 的长双歧杆菌和嗜酸乳杆菌组成。两种后生元都能通过螯合锌和铜离子有效地解聚淀粉样-β/Aβ-40 聚集体。后生元处理降低了半脑中内源性人 APP 蛋白表达和小鼠 APP 基因表达。此外，后生元处理还提高了线粒体 LONP1 活性。
我们的发现揭示了改善整个大脑记忆性能背后的不同机制：运动训练调节 NF-kB 信号通路，调节免疫反应，直到后生元减少 APP 基因表达，解聚现有的淀粉样-β 斑块，并激活海马体以外的大脑区域的线粒体蛋白质量控制；使用上述治疗方法可以互补并有效地减缓 AD 的发展。
