The Study: Exercise plasma boosts memory and dampens brain inflammation via clusterin

Overview: This study examined the effects of transfusing plasma from a group of “running” mice into a group of sedentary mice (those without an exercise wheel in their cage).

Key Points: 

Exercise has already been shown to be beneficial in slowing cognitive decline and neural degeneration although the precise mechanisms remain unclear.

The known cognitive benefits of physical activity appear related to reduced inflammation within the hippocampus. 

In previous studies, humans with cognitive impairment who participated in structured exercise programs for a period of six months demonstrated higher levels of the anti inflammatory protein Clusterin, thought to be associated with the known neural benefits of exercise. 

Analysis demonstrated a significant increase in Clusterin (an anti inflammatory protein) in the plasma of the running mice. Clusterin inhibits the expression of neuro inflammatory genes associated with both acute brain inflammation and Alzheimer’s disease. 

The authors then transfused plasma from the physically active mice into a matched group of inactive/sedentary mice. 

Following transfusion of exercise conditioned plasma, the sedentary mice demonstrated a reduction of both neuro inflammatory gene expression and induced brain inflammation as well as a two fold increase in the survival of newly produced astrocytes. 

This study demonstrates the possibility that some of the benefits of exercise may actually be transferrable when exercise conditioned plasma (containing anti inflammatory factors such as Clusterin) is transfused into more sedentary patients.

Author’s Conclusions: “Notably, these results are very similar to the direct effects of running…” 

Reviewer's Comments: In my mind there are two important things here: 

a) This study lends more understanding to the possible mechanisms by which exercise may benefit cognitive impairment and/or Alzheimer’s disease. 

b) This paper may pave the way for an exciting new approach to therapeutics for neurodegenerative disorders.

 Reviewer:  Mark R. Payne DC

Reference: Miguel Z, Khoury N, Betley M. et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature 2021 Dec 8.  doi: 10.1038/s41586-021-04183-x. Online ahead of print.

 Link To Abstract: https://pubmed.ncbi.nlm.nih.gov/34880498