Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice

Area of Science:

• Exercise Physiology
• Neuroscience
• Endocrinology

Background:

• Physical inactivity (PI) is linked to cognitive decline and depression.
• Exercise can ameliorate these effects, but the underlying mechanisms are unclear.
• Irisin, an exercise-induced myokine, may play a role in cognitive function.

Purpose of the Study:

• To investigate the association between irisin, cognitive decline, and mental deterioration in physically inactive mice.
• To determine if exercise-mediated improvements in cognitive function are dependent on irisin.
• To explore the impact of PI and exercise on irisin levels and related molecular pathways.

Main Methods:

• Mice were subjected to eight weeks of physical inactivity (PI) in confined cages.
• Regular exercise was administered to PI mice, with or without an irisin-neutralizing antibody.
• Measurements included physical parameters, behavioral tests (anxiety, depression, working memory), plasma irisin, and skeletal muscle/hippocampal gene expression (FNDC5, PPARGC1A, BDNF).

Main Results:

• PI induced anxiety, depression, and impaired working memory, along with increased epididymal fat mass.
• Regular exercise reversed these PI-induced deficits, increasing plasma irisin, FNDC5, PPARGC1A, hippocampal BDNF, and cell proliferation.
• Blocking irisin with an antibody attenuated the beneficial effects of exercise on cognitive function and hippocampal neurogenesis.

Conclusions:

• Exercise-inducible irisin is crucial for maintaining cognitive function and preventing mental deterioration during physical inactivity.
• Irisin positively correlates with working memory, hippocampal BDNF levels, and cell proliferation.
• Targeting irisin may offer a therapeutic strategy for cognitive impairments associated with physical inactivity.