Exercise Myokine Irisin Enables Behavioral Stress Resistance in Mice

Area of Science:

• Neuroscience
• Endocrinology
• Behavioral Science

Background:

• Physical activity confers stress resistance, but the underlying peripheral mechanisms are not fully understood.
• Irisin, a myokine released during exercise, is known for cognitive and neuroprotective effects.
• The role of irisin in mediating behavioral resistance to future stress is unexplored.

Purpose of the Study:

• To investigate if elevated peripheral irisin levels are sufficient to confer resistance to stress-induced behavioral changes.
• To examine the impact of forced peripheral irisin expression on anxiety-like behaviors in mice.
• To explore the relationship between irisin, brain-derived neurotrophic factor (Bdnf), and stress resilience.

Main Methods:

• Adeno-associated virus (AAV)-mediated peripheral expression of irisin or GFP control in adult male mice.
• Exposure to inescapable stress to induce anxiety-like behaviors.
• Assessment of social preference, locomotor activity, and circulating irisin levels.
• Measurement of brain-derived neurotrophic factor (Bdnf) expression and irisin receptor (integrin αV) in the dorsal raphe nucleus.

Main Results:

• AAV-mediated irisin expression significantly increased circulating irisin levels.
• Elevated irisin prevented stress-induced reductions in social preference without affecting general activity.
• Circulating irisin levels positively correlated with individual differences in sociability.
• Peripheral irisin elevation increased Bdnf expression in the brain.

Conclusions:

• Peripheral irisin is sufficient to confer behavioral resistance to future stress, independent of physical activity.
• Irisin may act via central neuroplasticity pathways, indicated by increased Bdnf expression.
• Irisin represents a potential prophylactic target for stress-related mental health disorders.