Voluntary Wheel Running Did Not Alter Gene Expression in 5xfad Mice, but in Wild-Type Animals Exclusively after One-Day of Physical Activity.

Anna Wierczeiko,Susanne Gerber,Lena Gammel,Kristina Endres,Hristo Todorov,Konstantin Radyushkin,Vu Thu Thuy Nguyen

doi:10.3390/cells10030693

Abstract

Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer’s disease (AD). However, the positive effect of therapeutic administration of physical activity has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different routines of physical activity in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute) and 30-day (chronic) voluntary wheel running and compared them with age-matched sedentary controls. We observed a significant increase in brain lactate levels in acutely trained 5xFAD mice relative to all other experimental groups. Subsequent brain RNA-seq analysis did not reveal major differences in transcriptomic regulation between training durations in 5xFAD mice. In contrast, acute training yielded substantial gene expression changes in wild-type animals relative to their chronically trained and sedentary counterparts. The comparison of 5xFAD and wild-type mice showed the highest transcriptional differences in the chronic and sedentary groups, whereas acute training was associated with much fewer differentially expressed genes. In conclusion, our results suggest that different training durations did not affect the global transcriptome of 3-month-old 5xFAD mice, whereas acute running seemed to induce a similar transcriptional stress state in wild-type animals as already known for 5xFAD mice.

Highlights

As the population ages, the number of people with degenerative diseases is simultaneously increasing
To better understand the molecular biology behind physical activity in Alzheimer’s disease (AD), we examined in this study the blood and brain lactate levels as well as the transcriptomes of 3-month-old transgenic 5xFAD and wild-type mice after one day or four weeks voluntary wheel running
To analyze the potential impact of acute and chronic physical voluntary training, we investigated male mice with the 5xFAD genotype and their wild-type littermates, starting at the age of 2 months

Summary

Introduction

The number of people with degenerative diseases is simultaneously increasing. Dementia is the fifth most frequent cause of death worldwide, with. Metabolic dysfunctions such as abnormal glucose uptake and brain insulin resistance, likely increasing degeneration and cognitive impairment, have been described in AD patients [8]. Besides the known pathological hallmarks, the leading cause of progressive brain atrophy is still unknown, explaining the lack of successful AD treatments. It became, generally accepted that the underlying mechanisms are polyfactorial and depend on the complex interplay of multiple (partly unknown) genetic and non-genetic variables [9,10,11,12]. Since prophylactic pharmacological therapies in advance of a possible disease outbreak might be ethically not reasonable or hampered by lack of a long-term compliance, lifestyle-modifying interventions, and preventions such as diet and physical activity have become increasingly attractive in the neurodegenerative research field

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Results

Conclusion