Exercise plasma boosts memory and dampens brain inflammation via clusterin
Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration 1 . The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus 2 – 4 , yet little is known about th...
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| Vydáno v: | Nature (London) Ročník 600; číslo 7889; s. 494 - 499 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
Nature Publishing Group UK
16.12.2021
Nature Publishing Group |
| Témata: | |
| ISSN: | 0028-0836, 1476-4687, 1476-4687 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration
1
. The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus
2
–
4
, yet little is known about the factors and mechanisms that mediate these effects. Here we show that ‘runner plasma’, collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a concerted increase in complement cascade inhibitors including clusterin (CLU). Intravenously injected CLU binds to brain endothelial cells and reduces neuroinflammatory gene expression in a mouse model of acute brain inflammation and a mouse model of Alzheimer’s disease. Patients with cognitive impairment who participated in structured exercise for 6 months had higher plasma levels of CLU. These findings demonstrate the existence of anti-inflammatory exercise factors that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans who engage in exercise.
Plasma from voluntarily running mice reduces baseline expression of neuroinflammatory genes and experimentally induced brain inflammation when infused into sedentary mice. |
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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contributions T.W.-C., T.A.R., Z.D.M. and M.B. designed and conceived the experiments. Z.D.M. and M.B. developed an initial paradigm of plasma transfer from runner to non-runner mice and studied the effect of plasma on neural stem cell activity. Z.D.M. and D.W. performed experiments to generate plasma pools, carried out animal treatments and processed brain tissue and plasma samples for molecular and protein analyses. D.W. performed and analysed behavioural experiments under the supervision of Z.D.M.; L.B., N.K., O.H. and Z.D.M. performed and analysed sequencing experiments. Z.D.M., N.L.S. and M.S. designed and performed behavioural experiments. N.K., A.Y., R.V., N.L. and Z.D.M. designed and performed experiments on BECs. N.K. performed statistical analysis and visualization of the single-cell datasets. H.Z. generated and provided the APP mice. D.L. performed retro-orbital injections of rCLU. L.Y., N.K. and Z.D.M. designed and performed experiments to assess the complement and coagulation cascades. B.L. performed statistical analyses and visualization of protein and gene datasets. J.K.F. performed experiments with humans and collected plasma samples. N.O., J.E.E., L.Z., P.L.M. and K.C. carried out MS analyses. Z.D.M., D.W. and T.W.-C. wrote the manuscript with input from T.A.R.; T.W.-C. and Z.D.M. supervised the study. |
| ISSN: | 0028-0836 1476-4687 1476-4687 |
| DOI: | 10.1038/s41586-021-04183-x |