Exercise plasma boosts memory and dampens brain inflammation via clusterin.
Level 5 - mechanism / opinion, no new human data
Preclinical animal transfer experiments combined with preliminary human cohort biomarker data
PubMed 34880498 · doi:10.1038/s41586-021-04183-x
What was done
Researchers collected plasma from voluntarily running mice ('runner plasma') and infused it into sedentary mice, assessing baseline and experimentally induced brain inflammation. Plasma proteomic profiling was conducted to identify circulating anti-inflammatory factors. They then intravenously administered clusterin (CLU), a complement cascade inhibitor identified in the screen, to mouse models of acute brain inflammation and Alzheimer's disease to measure endothelial binding and neuroinflammatory gene expression. Additionally, they measured plasma CLU levels in patients with cognitive impairment who completed a 6-month structured exercise intervention.
What was found
Infusion of runner plasma reduced baseline neuroinflammatory gene expression and experimentally induced brain inflammation in sedentary mice. Plasma proteomics showed an increase in complement cascade inhibitors, specifically CLU. Intravenously administered CLU bound to brain endothelial cells and decreased neuroinflammatory gene expression in both acute inflammation and Alzheimer's disease mouse models. Patients with cognitive impairment who completed 6 months of structured exercise showed higher plasma CLU levels. The abstract reports no numerical values or effect sizes.
Why it matters
This study identifies clusterin as a transferable exercise-induced blood factor that targets cerebrovascular endothelium to reduce neuroinflammation, providing a potential mechanism for exercise-induced cognitive protection.
Limits
The abstract provides no exact sample sizes for the mouse experiments or the human cohort. The core mechanistic findings rely on mouse models, which may not directly translate to human clinical outcomes. Long-term functional cognitive endpoints and clinical trial data in humans are not reported in the abstract.
Cited by
- supports Injecting blood plasma from exercised young mice into non-exercised mice transmits the beneficial effects of exercise on the brain.
- supports Exercise triggers the release of clusterin (apolipoprotein J) from the liver, and synthetic clusterin injected into mice mimics beneficial brain effects of exercise.