Exercise hormone irisin shields nerve cells in MS mouse study
Hormone released during exercise eased disease symptoms
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Mouse reserach shows the benefits of exercise.
- The exercise hormone irisin showed neuroprotective effects in a mouse model of multiple sclerosis.
- Irisin reduced nerve cell loss and eased clinical symptoms, suggesting a new therapeutic target.
- It protects neurons by activating a gene program.
The neuroprotective effects of exercise in multiple sclerosis (MS) may be aided by the irisin hormone.
A study showed irisin reduced nerve cell loss and eased clinical symptoms in a mouse model of the disease, making the hormone a potential new therapeutic target. And unlike existing MS therapies that target the immune system, it appears to act by boosting a protective gene program within nerve cells themselves, suggesting a new approach to halting neurodegeneration in MS.
“We are optimistic that our study will open up further developments of irisin as a therapeutic for, in particular, progressive MS,” study lead Christiane D. Wrann, PhD, a neuroscientist at Mass General Brigham Neuroscience Institute and the McCance Center for Brain Health, said in an institute press release. “Our findings strengthen the argument that irisin can help protect neurons in the context of multiple types of neurodegenerative diseases.”
The study, “The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis,” was published in Nature Metabolism.
Aerobic exercise is considered a potential disease-modifying intervention in MS, as it can improve physical fitness and slow the progression of neurological symptoms. Yet the exact biological mechanisms are not known, and no existing drug can replicate these effects.
Irisin benefits
Irisin has emerged as a promising candidate that may mediate part of the neuroprotective effects of exercise. Research has shown that exercise increases the activity of the gene that encodes the precursor protein of irisin in skeletal muscle and the brain, and raises irisin levels in the blood.
Wrann and colleagues previously showed that irisin can improve cognitive function and ease neuroinflammation in mouse models of Alzheimer’s disease. Similar research demonstrated the benefits of irisin in a mouse model of Parkinson’s disease.
The team set out to investigate the impact of irisin on MS progression in mice with experimental autoimmune encephalomyelitis, an induced disease commonly used to model MS.
Some animals were given free access to a running wheel for eight weeks before MS induction, while others had no access to a functional running wheel.
After MS induction, mice with access to voluntary free-wheel running exercise recovered more quickly from peak symptoms and showed less neuronal loss in the spinal cord. And the gene encoding irisin’s precursor protein was significantly increased in the calf muscles of running mice.
When the same protocol was applied to mice lacking the irisin gene, there was no improvement in MS symptoms or reduction in neuronal loss in exercised animals compared with sedentary mice. The findings suggested that “irisin is required for the neuroprotective effects of voluntary running in the [MS] model,” the team wrote.
To test whether an irisin-based treatment could protect against neurodegeneration, mice were injected with a viral vector carrying the irisin gene on the day of MS induction. This led to improved recovery from peak MS symptoms, reduced neuronal loss in the spinal cord, and less immune cell infiltration.
While control MS mice lost the ability to distinguish between different environments in a memory test, irisin treatment restored this ability. In the hippocampus, a brain region involved in memory, neuron loss was also reduced with irisin treatment.
Additional experiments showed that irisin’s neuroprotective effects in MS were not mediated by changes in immune responses but rather by the activation of neuronal genes involved in neuroprotection.
“We did not find a direct suppressive effect of irisin on peripheral immunity, but rather direct neuroprotective effects,” said Ruxandra F. Sîrbulescu, PhD, co-senior author on the study and a neuroimmunologist at Mass General Brigham Neuroscience Institute.
Imaging studies of MS spinal cord tissue detected a loss of synapses, the junctions where neurons communicate with one another. This loss, however, was rescued in both irisin-treated mice and in MS mice that had undergone voluntary running. The function of mitochondria, the cell’s energy producers, also improved in treated and running mice.
The researchers then confirmed that irisin directly binds to motor neurons in the spinal cord.
“What we find particularly exciting is that an exercise-induced molecule can directly protect neurons in a mouse model of multiple sclerosis, revealing a fundamentally new mechanism by which exercise can influence neurodegeneration in MS,” said Sina C. Rosenkranz, MD, first author of the study and head of the behavioral interventions group at the Institute for Neuroimmunology and Multiple Sclerosis at the University Medical Center Hamburg-Eppendorf.
“Our results from using irisin in a therapeutic regimen strongly support irisin as an attractive drug target to counteract neurodegeneration in the progressive phase of MS, pending validation in future studies,” the team concluded.
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