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Editor | xi The nervous system controls all our behaviors, so it is important to maintain the stability of its structure and function, but how to maintain its stability is still poorly understood
.
Previous studies have shown that the lactic acid produced by glial cells can provide energy metabolism support for neurons, and it has been found that blocking the oligodendrocyte-neuronal lactic acid transport process is related to neurodegeneration
.
However, the key regulatory mechanism of lactate metabolism in glial cells and its relationship with neuron/axon function are still unclear
.
On October 6, 2021, a research team led by Professor Xiao Bo from the School of Life Sciences of Southern University of Science and Technology published an article Rheb-regulated mitochondrial pyruvate metabolism of Schwann cells linked to axon stability in the Journal of Developmental Cell, and found that peripheral glial cells-Schwann The pyruvate-lactic acid conversion metabolism regulated by Rheb in cells is very important for maintaining the stability of axons in the peripheral nervous system
.
The research team previously discovered that Rheb can dynamically enter mitochondria and regulate mitochondrial energy metabolism (see BioArt report: Dev Cell | Xiao Bo's team discovered a new mechanism for cells to regulate mitochondrial energy metabolism, which interprets cell activation of mTORC1 and neural activity coupled with energy metabolism Provide a new perspective), and then use genetic means to knock out the Rheb gene in Schwann cells, and found that the inactivation of Rheb gene will hinder the process of mitochondrial pyruvate dehydrogenase (PDH) converting pyruvate into acetyl-CoA, enhancing acetone Conversion of acid to lactic acid
.
The lactic acid transported by Schwann cells to neurons will be rapidly metabolized into pyruvate in the cytoplasm and mitochondria, which participates in mitochondrial energy metabolism
.
This study found that an increase in neuronal lactic acid intake will lead to an increase in mitochondrial energy metabolism, produce more reactive oxygen species (ROS), and lead to neuronal oxidative stress
.
Oxidative stress damages mitochondria and ATP synthesis, which leads to the production of more reactive oxygen species
.
This vicious circle eventually leads to the degeneration of axons in the peripheral nervous system
.
In order to further prove that the increased metabolism of lactic acid in Schwann cells is the root cause of peripheral nerve damage, the research team used pharmacological methods to inhibit the production and transport of lactic acid and found that it can effectively prevent peripheral nerve damage
.
In addition, they also found that knocking out Rheb in Schwann cell precursor cells has only a weak effect on the formation of Schwann cells and peripheral myelin development, which further proves that the increase in lactate caused by Rheb knockout is the main cause of peripheral nerve damage.
Reason
.
Lactic acid can be used as an energy substrate to support the function of neurons, protect damaged axons, and promote axon regeneration
.
However, this study shows that long-term excessive intake of lactic acid by neurons can cause peripheral nerve damage, indicating that lactic acid may be a "double-edged sword" for neurons
.
Usually, lactic acid is abnormally increased in disease states such as diabetes and brain aging.
Therefore, this study may provide new ideas for elucidating the pathogenesis of aging and neurodegenerative diseases
.
Professor Xiao Bo and his student Jia Lanlan (the first author, a graduate student of the State Key Laboratory of Biotherapy of Sichuan University, and a visiting student of Southern University of Science and Technology) conceived and designed this research
.
Jia Lanlan completed most of the experiments
.
Original link: https://doi.
org/10.
1016/j.
devcel.
2021.
09.
013 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
.
Previous studies have shown that the lactic acid produced by glial cells can provide energy metabolism support for neurons, and it has been found that blocking the oligodendrocyte-neuronal lactic acid transport process is related to neurodegeneration
.
However, the key regulatory mechanism of lactate metabolism in glial cells and its relationship with neuron/axon function are still unclear
.
On October 6, 2021, a research team led by Professor Xiao Bo from the School of Life Sciences of Southern University of Science and Technology published an article Rheb-regulated mitochondrial pyruvate metabolism of Schwann cells linked to axon stability in the Journal of Developmental Cell, and found that peripheral glial cells-Schwann The pyruvate-lactic acid conversion metabolism regulated by Rheb in cells is very important for maintaining the stability of axons in the peripheral nervous system
.
The research team previously discovered that Rheb can dynamically enter mitochondria and regulate mitochondrial energy metabolism (see BioArt report: Dev Cell | Xiao Bo's team discovered a new mechanism for cells to regulate mitochondrial energy metabolism, which interprets cell activation of mTORC1 and neural activity coupled with energy metabolism Provide a new perspective), and then use genetic means to knock out the Rheb gene in Schwann cells, and found that the inactivation of Rheb gene will hinder the process of mitochondrial pyruvate dehydrogenase (PDH) converting pyruvate into acetyl-CoA, enhancing acetone Conversion of acid to lactic acid
.
The lactic acid transported by Schwann cells to neurons will be rapidly metabolized into pyruvate in the cytoplasm and mitochondria, which participates in mitochondrial energy metabolism
.
This study found that an increase in neuronal lactic acid intake will lead to an increase in mitochondrial energy metabolism, produce more reactive oxygen species (ROS), and lead to neuronal oxidative stress
.
Oxidative stress damages mitochondria and ATP synthesis, which leads to the production of more reactive oxygen species
.
This vicious circle eventually leads to the degeneration of axons in the peripheral nervous system
.
In order to further prove that the increased metabolism of lactic acid in Schwann cells is the root cause of peripheral nerve damage, the research team used pharmacological methods to inhibit the production and transport of lactic acid and found that it can effectively prevent peripheral nerve damage
.
In addition, they also found that knocking out Rheb in Schwann cell precursor cells has only a weak effect on the formation of Schwann cells and peripheral myelin development, which further proves that the increase in lactate caused by Rheb knockout is the main cause of peripheral nerve damage.
Reason
.
Lactic acid can be used as an energy substrate to support the function of neurons, protect damaged axons, and promote axon regeneration
.
However, this study shows that long-term excessive intake of lactic acid by neurons can cause peripheral nerve damage, indicating that lactic acid may be a "double-edged sword" for neurons
.
Usually, lactic acid is abnormally increased in disease states such as diabetes and brain aging.
Therefore, this study may provide new ideas for elucidating the pathogenesis of aging and neurodegenerative diseases
.
Professor Xiao Bo and his student Jia Lanlan (the first author, a graduate student of the State Key Laboratory of Biotherapy of Sichuan University, and a visiting student of Southern University of Science and Technology) conceived and designed this research
.
Jia Lanlan completed most of the experiments
.
Original link: https://doi.
org/10.
1016/j.
devcel.
2021.
09.
013 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
