Exercise combined with postbiotics treatment results in synergistic improvement of mitochondrial function in the brain of male transgenic mice for Alzheimer's disease

• Published in: BMC neuroscience 2023-12, Vol.24 (1), p.68-68, Article 68
• Main Authors: Kolonics, Attila, Bori, Zoltán, Torma, Ferenc, Abraham, Dora, Fehér, János, Radak, Zsolt
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Animals; ATP-Dependent Proteases - metabolism; Bifidobacterium longum; Brain - metabolism; Care and treatment; Cognitive function; Copper; Dehydrogenases; Dietary supplements; Disaggregation; Disease Models, Animal; Exercise; Exercise therapy; Fitness equipment; Fitness training programs; Gene expression; Gut microbiota; Health aspects; Hippocampus; Hippocampus - metabolism; Humans; Immune response; Laboratories; Lactobacillus acidophilus; Male; Metabolism; Metabolites; Mice; Mice, Transgenic; Microbiota; Microbiota (Symbiotic organisms); Mitochondria; Mitochondrial protein quality control; Mitochondrial Proteins - metabolism; Neurodegenerative diseases; Neuroprotection; NF-kappa B - metabolism; NF-κB protein; Physical training; Plaque, Amyloid - metabolism; Plaques; Presenilin 1; Presenilin-1 - genetics; Quality control; Running; Signal transduction; Testing; Transgenic animals; Transgenic mice; Zinc; β-Amyloid
• ISSN: 1471-2202; 1471-2202
• 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.