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Written | As the old saying goes, life lies in sports
.
In addition to helping us maintain a good body shape, exercise has many invisible benefits to human health, such as slowing down cognitive aging and improving neurodegenerative diseases
.
It is currently believed that exercise is likely to play a role in the brain by reducing inflammation in the nervous system [1], but the specific molecular mechanism is still unclear
.
Researchers speculate that during exercise, muscles or other tissues may release certain "motor factors" into the blood to act on the brain
.
For example, studies have reported that exercise-induced plasma protein-GPDL1 can improve the cognitive ability of elderly mice [2]
.
However, it is still unclear whether there are other "motor factors" that can directly affect the brains of young mice
.
On December 8, 2021, a research team led by Tony Wyss-Coray from the Department of Neurology and Neuroscience at Stanford University School of Medicine published a research article titled Exercise plasma boosts memory and dampens brain inflammation via clusterin on Nature, revealing The complement and coagulation protein clusterin in the blood of exercise mice can improve the cognitive ability of mice by reducing inflammation in the nervous system
.
In order to explore whether the blood of exercise mice can help improve cognition, the authors took exercise mice (bred in a cage with a runner for 28 days) and control mice's plasma (denoted as RP and CP) and injected them.
Into young recipient mice that are not exercising
.
The results showed that RP increased the number of neuronal cells, neuroblasts and astrocytes in recipient mice
.
In addition, behavioral experiments also showed that the spatial learning ability and memory ability of the recipient mice injected with RP were also improved
.
These results indicate that the blood of exercise mice can indeed help improve cognition
.
In order to clarify the molecular basis of this effect, the authors performed RNA-seq analysis on the hippocampus of mice treated with RP and CP, and the results showed that RP treatment down-regulated the expression of inflammatory genes in the hippocampus of young mice
.
Furthermore, the author used LPS treatment to simulate the nervous system inflammation associated with neurodegenerative diseases, and the results once again proved that RP can effectively antagonize the hippocampal neuroinflammation caused by LPS
.
In order to find out which "motor factor" in the blood plays a key role, the author conducted a proteomic analysis of RP and CP, and found that complement and coagulation pathways are activated in RP, suggesting that complement and coagulation pathways may be Play an important role in this process
.
Next, the author takes the four most differentially expressed proteins in RP-CLU (clusterin), FH (Complement factor H), PEDF (pigment epithelium-derived factor) and LIFR (leukaemia inhibitory factor receptor) through immunoadsorption methods After removing them from RP, the results show that only after removing CLU, the anti-inflammatory ability of RP is greatly reduced
.
Interestingly, LRP8, the main receptor of CLU, is highly expressed in brain endothelial cells and neurons, and the author proved that CLU in blood circulation can be combined with LRP8 in the brain, suggesting that CLU in blood circulation can directly Act on the brain to function
.
Finally, the author verified the anti-inflammatory ability of CLU in AD model mice (APP mice), and the results showed that injection of recombinant CLU protein (rCLU) can effectively reduce chronic inflammation of the nervous system in AD mice
.
In addition, consistent with the results of the mouse study, the authors found that the level of CLU was also significantly increased in people with moderate cognitive impairment during exercise
.
In summary, the study revealed a new "motor factor"—clusterin improves the cognitive ability of mice by reducing inflammation in the nervous system
.
The results of this study may provide us with new insights into how exercise can benefit the brain
.
Original link: https://doi.
org/10.
1038/s41586-021-04183-x Plate maker: 11 References 1.
Gleeson, M.
et al.
The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease.
Nat.
Rev.
Immunol.
11, 607–615 (2011).
2.
Horowitz, AM et al.
Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain.
Science 369, 167–173 (2020).
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
.
In addition to helping us maintain a good body shape, exercise has many invisible benefits to human health, such as slowing down cognitive aging and improving neurodegenerative diseases
.
It is currently believed that exercise is likely to play a role in the brain by reducing inflammation in the nervous system [1], but the specific molecular mechanism is still unclear
.
Researchers speculate that during exercise, muscles or other tissues may release certain "motor factors" into the blood to act on the brain
.
For example, studies have reported that exercise-induced plasma protein-GPDL1 can improve the cognitive ability of elderly mice [2]
.
However, it is still unclear whether there are other "motor factors" that can directly affect the brains of young mice
.
On December 8, 2021, a research team led by Tony Wyss-Coray from the Department of Neurology and Neuroscience at Stanford University School of Medicine published a research article titled Exercise plasma boosts memory and dampens brain inflammation via clusterin on Nature, revealing The complement and coagulation protein clusterin in the blood of exercise mice can improve the cognitive ability of mice by reducing inflammation in the nervous system
.
In order to explore whether the blood of exercise mice can help improve cognition, the authors took exercise mice (bred in a cage with a runner for 28 days) and control mice's plasma (denoted as RP and CP) and injected them.
Into young recipient mice that are not exercising
.
The results showed that RP increased the number of neuronal cells, neuroblasts and astrocytes in recipient mice
.
In addition, behavioral experiments also showed that the spatial learning ability and memory ability of the recipient mice injected with RP were also improved
.
These results indicate that the blood of exercise mice can indeed help improve cognition
.
In order to clarify the molecular basis of this effect, the authors performed RNA-seq analysis on the hippocampus of mice treated with RP and CP, and the results showed that RP treatment down-regulated the expression of inflammatory genes in the hippocampus of young mice
.
Furthermore, the author used LPS treatment to simulate the nervous system inflammation associated with neurodegenerative diseases, and the results once again proved that RP can effectively antagonize the hippocampal neuroinflammation caused by LPS
.
In order to find out which "motor factor" in the blood plays a key role, the author conducted a proteomic analysis of RP and CP, and found that complement and coagulation pathways are activated in RP, suggesting that complement and coagulation pathways may be Play an important role in this process
.
Next, the author takes the four most differentially expressed proteins in RP-CLU (clusterin), FH (Complement factor H), PEDF (pigment epithelium-derived factor) and LIFR (leukaemia inhibitory factor receptor) through immunoadsorption methods After removing them from RP, the results show that only after removing CLU, the anti-inflammatory ability of RP is greatly reduced
.
Interestingly, LRP8, the main receptor of CLU, is highly expressed in brain endothelial cells and neurons, and the author proved that CLU in blood circulation can be combined with LRP8 in the brain, suggesting that CLU in blood circulation can directly Act on the brain to function
.
Finally, the author verified the anti-inflammatory ability of CLU in AD model mice (APP mice), and the results showed that injection of recombinant CLU protein (rCLU) can effectively reduce chronic inflammation of the nervous system in AD mice
.
In addition, consistent with the results of the mouse study, the authors found that the level of CLU was also significantly increased in people with moderate cognitive impairment during exercise
.
In summary, the study revealed a new "motor factor"—clusterin improves the cognitive ability of mice by reducing inflammation in the nervous system
.
The results of this study may provide us with new insights into how exercise can benefit the brain
.
Original link: https://doi.
org/10.
1038/s41586-021-04183-x Plate maker: 11 References 1.
Gleeson, M.
et al.
The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease.
Nat.
Rev.
Immunol.
11, 607–615 (2011).
2.
Horowitz, AM et al.
Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain.
Science 369, 167–173 (2020).
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
