Treadmill Exercise Changes the Landscape of a Diseased Brain

By Matthew Lee ‘21

amyloid.jpg

Figure 1. Amyloid deposits in the walls of blood vessels

Alzheimer’s disease (AD) and other neurodegenerative diseases have debilitating effects on the elderly. AD is characterized by the buildup of proteins, subtype amyloid beta (Aβ), which form plaques and can contribute to Tau build up. However, there are multiple means by which to reduce the likelihood of developing AD. Several studies have confirmed the beneficial effects of exercise on mice with AD.  Dr. Jing Zhang of Shandong University and a team of researchers investigated the possible mechanisms behind these effects.

The sample mice were divided into four groups – sedentary control, exercise (trained) control, sedentary transgenic APP, and exercise transgenic APP – with the trained condition characterized by treadmill exercise for 5 months. APP transgenic mice are considered the standard rodent model for investigating AD. The results showed increased fraction of neuronal density by ~3% in the hippocampus and neocortex of trained mice, suggesting some regenerative capacity. The propagation of astrocytes, a star shaped glial cell, in both regions also decreased by a factor of 2 in trained mice, suggesting a correlation between astrocyte distribution and amyloid beta domains distribution.  

It is known that APP mice develop amyloid precursor proteins quicker compared to wild type mice, resulting in rapid neurodegeneration. However, trained APP mice had significantly less plaque in both the hippocampus (~150/mm2 difference) and neocortex (~600/mm2 difference) compared to sedentary APP mice. Lastly, gene expression pertaining to APP were monitored and it was found that long term exercise reduced APP expression as well as the genes of other molecules associated with APP degradation and transport.

Exercise seems to have numerous effects on amyloid beta regions and associated glia, particularly astrocytes, as well as the metabolism of APP itself. Future studies should build on these findings and focus on the exact mechanisms by which such changes alter gene expression and cell distribution. Increasing our understanding of the processes influencing neurodegeneration is imperative to further develop effective therapies and preventive measures.  

 

References:

  1. J. Zhang, et. al., Long-term treadmill exercise attenuates Aβ burdens and astrocyte activation in APP/PS1 mouse model of Alzheimer’s disease. Neuroscience Letter 666, 70-77 (2018). doi: 10.1093lnarlgky094
  2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_very_high_mag.jpg
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