Exercise plasma boosts memory and dampens brain inflammation via clusterin.

Area of Science:

• Neuroscience
• Immunology
• Exercise Physiology

Background:

• Physical exercise benefits cognitive health, slowing aging and neurodegeneration.
• Exercise-induced cognitive benefits are linked to hippocampal plasticity and reduced inflammation.
• Mechanisms mediating exercise's brain benefits remain largely unknown.

Purpose of the Study:

• To identify transferable factors in exercise plasma that reduce neuroinflammation.
• To investigate the role of clusterin (CLU) in mediating exercise's anti-inflammatory effects on the brain.
• To explore the presence of these factors in humans with cognitive impairment.

Main Methods:

• Infusion of 'runner plasma' from exercising mice into sedentary mice.
• Plasma proteomic analysis to identify key proteins, focusing on complement cascade inhibitors.
• Intravenous injection of clusterin (CLU) in mouse models of brain inflammation and Alzheimer's disease.
• Analysis of plasma CLU levels in human patients with cognitive impairment undergoing exercise.

Main Results:

• Runner plasma reduced baseline and induced neuroinflammatory gene expression in sedentary mice.
• Clusterin (CLU) was identified as a key complement cascade inhibitor increased by exercise.
• Injected CLU bound to brain endothelial cells and reduced neuroinflammation in mouse models.
• Humans with cognitive impairment showed elevated plasma CLU after 6 months of exercise.

Conclusions:

• Exercise plasma contains transferable anti-inflammatory factors targeting the cerebrovasculature.
• Clusterin (CLU) is a key mediator of these exercise-induced neuroprotective effects.
• Elevated CLU levels in humans suggest a conserved mechanism linking exercise, inflammation, and cognitive health.