Exercise and Probiotics Attenuate the Development of Alzheimer Disease in Mice

It has been suggested that the gut-brain axis could play a significant role in the development of neurodegenerative diseases. Therefore, normalization of gut microbiota (microbiome) could be important and influence the development of Alzheimer Diseases (AD). The genome of microbiome is 100 fold larger than the human genome, and microbial compounds give the major input to the bidirectional communication between the enteral neuron-immune system and the brain. Based on the currently available scientific information, we propose that exercise training and probiotic treatments could delay inflammation, ameliorate oxidative stress, and decrease levels of beta amyloids, thereby attenuating loss in brain function. It is hypothesized that probiotic treatment alone and combined with exercise training could beneficially effect microbiome and delay the development of AD. Experimental design A total thirty six of 32 APP/PS1 transgenic male mice were divided into control (C), 20 week treadmill running trained (T) 20 week probiotic supplemented (Framelim) (P) and combined treated (TP) groups respectively. Results Cognitive test revealed the continuous development in the performance of the animals on combined treatment. During Morris Water Maze test, on the second day the animals showed significantly better performance, the 3rd and 4th day revealed a tendency for improved learning skills compared to the control group. 6E10 immunohistochemistry against beta-amyloid plaques revealed, that the number of plaques in hippocampus in the exercise group were significantly lower than in the control and combined group. The plaque area in the hippocampus was significantly lower in all treated groups when it compared to the control group. This suggests an absence of direct link between cognitive function and the number of plaques. We observed an increased number of astrocytes around the plaques, however significant differences in the density of astrocytes in different groups were not found. Data revealed that exercise training increased DNA repair, hence could attenuated the cell death associated with AD. Our results confirm that physical exercise and the use of probiotics can ameliorate cognitive function in AD via alteration of microbiome.