Irisin injection mimics exercise effects on the brain proteome.

Physical inactivity can endanger human health and increase the incidence of neurodegenerative disease. Exercise has tremendous beneficial effects on brain health and cognitive function, especially in older adults. It also improves brain-related outcomes in depression, epilepsy and neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. Irisin is a mediator of the beneficial effects of exercise. This study aimed to assess the proteome alterations in adult male National Maritime Research Institute (NMRI) mice brain tissue upon three different conditions including endurance exercise, resistance exercise and irisin injection. Quantification of irisin levels in blood was performed using irisin-ELISA Kit. Quantification and identification of proteins via two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)/MS showed the alteration of at least 21 proteins due to different treatments. Cellular pathway analysis revealed common beneficial effects of sole irisin treatment and different exercise procedures suggesting the capability of irisin injection to substitute the exercise when physical activity is not possible.

Comparative proteome analyses highlight several exercise-like responses of mouse sciatic nerve after IP injection of irisin.

Many beneficial effects of exercise on the nervous system are mediated by hormone (growth factor)/receptor signaling. Considering the accumulating evidence on the similarity of some beneficial effects, irisin can be a proposed effector of exercise; however, the mechanism underlying these effects remains largely unknown. More evidence on the mechanism of action might reveal its potential as a treatment strategy to substitute exercise recovery protocols for nerve injuries in physically disabled patients. To evaluate the underlying mechanism of irisin involvement in nerve adaptation and exerting beneficial effects, we studied the proteome profile alteration of mouse sciatic nerve after irisin administration. We also compared it with two 8-week protocols of resistance exercise and endurance exercise. The results indicate that irisin contributes to the regulation of nerve metabolism via overexpression of Ckm and ATP5j2 proteins. Irisin administration may improve sciatic nerve function by maintaining the architecture, enhancing axonal transport, and promoting synapse plasticity through increased structural and regulatory proteins and NO production. We also showed that irisin has the potential to induce neurotrophic support on the sciatic nerve by maintaining cell redox homeostasis, and responses to oxidative stress via the upregulation of disulfide-isomerase and superoxide dismutase enzymes. Comparing with exercise groups, these effects are somewhat exercise-like responses. These data suggest that irisin can be a promising therapeutic candidate for specific targeting of defects in peripheral neuropathies and nerve injuries as an alternative for physical therapy.