Exercise and neurodegenerative disease
The Wrann team also found this irisin appears to play a role in protecting against neurodegeneration. The researchers raised mice that did not have irisin and had Alzheimer’s-like symptoms. These double-affected mice experienced symptoms faster than mice with Alzheimer’s disease alone and showed cognitive improvements when irisin production was restored.
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Wrann suspects that one way irisin helps because it reduces inflammation caused by the malfunction of the brain’s immune system. This system consists mainly of cells called microglia and astrocytes, which are usually responsible for reducing brain infection and cleaning up debris after injury. However, with the age of mammals, these cells can remain active once the acute danger has passed and interfere with neuronal function by first breaking the connections between neurons and then killing the cells themselves.
This activity causes chronic brain inflammation, which is associated with many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. But irisin-treated laboratory mice had less inflammation in their hippocampus and their microglia and astrocytes were reduced, suggesting that irisin helped to limit the intermittent immune response.
Are these results applicable to humans? Perhaps based on preliminary work done in Wrann’s lab by other teams. Irisin has an identical molecular structure in mice and humans, he said, suggesting that it performs similar functions in both species.
The results have interesting implications for the neurological benefits of exercise studies show elevated levels of irisin in people’s blood after exercise. On the other hand, postmortem brain analyzes of Alzheimer’s patients revealed a 70% reduction in the irisin precursor molecule compared to age-appropriate controls, suggesting that irisin may be neuroprotective.
From a therapeutic point of view, “irisin is certainly promising,” says Hanshin, “especially given the data on its effect on the brain.” But he warns that irisin has not yet passed the tests that are being conducted to develop drugs. “Whether this works in humans remains to be seen.”
Depression, anxiety and mood disorders
Handschin is interested in the interactions between muscles, exercise, mood and motivation. In an unpublished paper, his group investigated the effect that some molecules produced by trained muscles have on the desire of mice to run on a treadmill. Animals that do not have these factors are able to run, but choose not to do so, an unusual behavior for mice, which usually run nearly 10 kilometers a day.
“There must be something in the muscle that sends signals to the brain and somehow reduces the urge to run,” Hendshin concluded.
The promise of this area for the treatment of mood disorders (especially severe depression) is also of interest to Spiegelman, who calls it one of the great unmet needs of medicine. “The Great Depression is the leading cause of suicide and is especially common in young people,” he said. He and colleagues are currently evaluating the effects of iris on anxiety-induced depression in experimental mouse models.
. the brain’s conversation during exercise is not limited to muscles. Its interaction with molecules (mainly proteins) secreted by the liver, fats and bones remodels the brain to sharpen our thinking, avoid depression, etc.
With viable candidates for drugs such as irisin and others on the horizon, the University of Alabama’s Rodriguez believes that “we are on the verge of a great era of discovery that will finally be transferred to the clinic.”
But the explosion of research into cross-muscle and brain disorders offers both rewards and challenges, said Carina Alvinya, an associate professor of neuroscience at the University of Florida School of Medicine. The most prominent molecules affect many systems in many ways, which means that their potential range is huge, but unraveling their various dependencies can be a headache. Creating a drug that has no unintended consequences will be a big challenge, he said.
However, Alvinia finds hope in the research she and others are doing, as it suggests that “the environment and our lifestyle choices can have a big impact on how we age,” Alvinia said. This means that it is up to us to age healthier and maintain a higher quality of life for longer.
“So, if I had to say one thing, it would be: stay active, even if it’s just walking a few minutes a day. If you can, do it.”