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

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.

Multi-omics studies reveal ameliorating effects of physical exercise on neurodegenerative diseases

“…The genomics analysis showed that exercise enhanced the AD model mice’s gene expression of BDNF ( Alvarez-Lopez et al, 2013 ) and Glial fibrillary acidic protein (GFAP, participating in the formation and maintenance of cytoskeleton tension; Wierczeiko et al, 2021 ) in the hippocampus. It also increased the expression of vacuolar protein sorting 52 (VPS52) in MCI participants.…”

“…The risk of AD is 60-80% dependent on heritable factors, with more than 40 AD-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with it (Scheltens et al, 2021). Accumulated clinical data support that the core cerebrospinal fluid (CSF) biomarkers, amyloid β (Aβ42), total Tau (T-Tau) and phosphorylated Tau (P-Tau), reflect key Metabolomics (Wang et al, 2021; Microbiomics (Wang et al, 2021) Genomics (Wierczeiko et al, 2021) Proteomics (Wang et al pathophysiological factors in AD (Blennow and Zetterberg, 2018). Biomarkers are of great significance for the diagnosis and prevention of AD and for observing the effect of exercise intervention.…”