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Image credit: pixabay The human body is like a fertile soil - soil that can "grow" cells
.
Our skin, blood, bones, and many other organs continue to grow new cells throughout our lives
.
However, one organ may be an exception - the brain
.
Author | 27 Reviewer | clefable If you search for "neurons" and "regeneration", you may find some contradictory results, and may even be posted by the same media
.
Take "Universal Science" itself as an example.
In 2018, we reprinted an article entitled "Nature: After Adulthood, Does the Brain Stop Making New Neurons?" ", but less than a month later, we reprinted another article entitled "Refuting Nature! Cell sub-issue: Elderly people can generate "new brain cells".
.
.
" article
.
Is either of these two articles "wrong"? Not so
.
In fact, the question of whether human beings can form new brain neurons in adulthood has been debated passionately for nearly a hundred years, and a unified answer has not been obtained until today
.
Neurogenesis of Neurons In 1928, Santiago Ramón y Cajal, known as the "pioneer of modern neuroscience", declared that the human brain would never form new neurons after adulthood
.
Over the next few decades, this assertion quickly became mainstream thought in academia
.
Until the 1980s and 1990s, many neuroscientists gradually discovered that new neurons can still be formed in the adult rodent and non-human primate brains, a process known as "neurogenesis"
.
In mammals, adult neurogenesis is concentrated in two regions: the hippocampus, which is responsible for learning and memory, and the olfactory bulb, which is responsible for smelling
.
Neurons in the hippocampus (red) | Credit: Thomas Deerinck, NCMIR/SPL 1998 Fred Gage and colleagues at the Salk Institute in Nature Medicine A classic study was published
.
They used a substance called bromodeoxyuridine (BrdU), which is similar to nucleosides and can be taken up by cells when they divide, and is involved in forming the DNA of new cells
.
In this way, BrdU becomes a "tag" for new cells
.
At the time, doctors would use the substance to measure the rate at which cancer cells formed, while Gage and his colleagues wanted to see if neurons were "tagged
.
"
The results directly contradict previous "mainstream thinking": the substance was found in the brains of all five cadaveric donors and was concentrated in the dentate gyrus region of the hippocampus
.
This suggests that the cells here did not divide until after the injection of BrdU—that is, the formation of new neurons in the brain
.
Hippocampus (top) and BrdU-labeled nuclei (bottom arrow) (Image source: PS Eriksson et al.
, 1998) Indeed, more and more scholars have begun to agree with this view, but there are also many scholars who disagree on this Research has raised doubts
.
Some have questioned that Gage et al.
did not examine all neurons, possibly mixing in other regenerative cells
.
In addition, since BrdU injections into humans were quickly banned, there was a lack of evidence to replicate the experiments
.
Although the nuclear explosion is controversial, the 1998 study opened the door to the study of neurogenesis in the human brain, and more and more neuroscientists began to pay attention to this question and try to give their own answers - of course, their answers Also often very different
.
In an interesting study, published in Cell in 2013, Jonas Frisén and colleagues at Karolinska Institutet in Sweden used the nuclear explosions of the 1950s and 1960s.
Residues of experiments to study neurogenesis in the human brain
.
Specifically, Friesen's research ideas are similar to Gage's, and they are all trying to introduce markers to "label" the newborn cells
.
After all, synthesizing DNA is something that almost every cell does before dividing.
As long as these markers are detected in cellular DNA, it means that there are "new cells"
.
This time, Friesen and colleagues used a marker called "nuclear carbon
.
"
Image source: pixabay Nuclear explosion carbon, as the name suggests, comes from nuclear explosion
.
From 1945 to 1963, many countries conducted large-scale surface nuclear explosion tests.
These explosions more than doubled the concentration of the radioactive carbon isotope in the atmosphere - carbon 14, which is called "nuclear explosion carbon"
.
After the nuclear test ban treaty was signed in 1963, the amount of carbon-14 in the atmosphere began to steadily decline due to the dilution effect of the Earth's carbon cycle
.
Today, carbon-14 levels in the atmosphere have largely fallen back to 1950s levels
.
Carbon 14 in the atmosphere enters the human body along the food chain
.
When we divide new cells, these "nuclear explosions" are unknowingly integrated into the newly synthesized DNA and become the "age markers" of the new cells
.
For example, if some cells were formed in 1960, they must have higher carbon-14 content than cells formed in the last two years
.
What Friesen and his colleagues have to do is to use a mass spectrometer to analyze the carbon-14 content of neurons in different areas of the brain, and compare the historical changes in atmospheric carbon-14 concentration to know whether new cells are added to these cells, or even Can be accurate to the year
.
The black line in the figure is the carbon-14 concentration in the atmosphere, the red dot is the carbon-14 concentration in the DNA of non-neuronal cells, and the abscissa is the birth year of the deceased donor
.
In the picture, the carbon-14 concentration in the DNA of the donors born before the large-scale nuclear test was above atmospheric levels, while the DNA of the donors born after the large-scale nuclear test was below the atmospheric level, which means that the measured cells are constantly "renewing" ( Image credit: KL Spalding et al.
, 2013) In Friesen's previous study, carbon-14 levels in all 14 olfactory bulbs examined were largely consistent with the levels of carbon-14 in the atmosphere at the time of the donor's birth
.
That is, the neurons in the olfactory bulb are not "replaced" after birth
.
This time, however, Friesen found that the situation in the hippocampus was completely different
.
The research team looked at the brains of donors of different ages and measured carbon-14 levels in neurons in different regions of the hippocampus
.
To get a more precise understanding of when and how quickly neurons "update", the researchers simulated a number of possible scenarios and compared them with their measurements
.
The results showed that neurons in the dentate gyrus region of the hippocampus of the brain continue to renew even in adulthood
.
Using carbon-14-labeled cell ages, the researchers compared the proportion of "renewal" neurons in donors by birth date, and roughly estimated that we generate about 1,400 new neurons per day
.
The black line in the figure is the atmospheric carbon-14 concentration, and the blue point is the carbon-14 concentration of the neuronal DNA in the dentate gyrus region of the hippocampus, showing a trend similar to that of non-neuronal cell DNA (Image source: KL Spalding et al.
, 2013 ) Contradictory Research Yet the story is not over
.
As mentioned before, research on whether brain neurons can regenerate is endless, and the academic community basically agrees on the olfactory bulb (that is, the olfactory bulb cannot generate new neurons in adulthood), but the controversy about the hippocampus has continued
.
The two articles we mentioned at the beginning are a good example
.
In March 2018, a study published in Nature used fluorescent markers to label possible "new cells" and took a closer look at cell morphology, but did not find any neurons in a "young" state
.
However, less than a month later, Cell Stem Cell published an article with the exact opposite result
.
For the first time, the researchers looked at neurons in the hippocampus shortly after an individual's death, also stained with fluorescent markers, and thought they had found large numbers of immature neuronal and interneuron progenitors
.
Some neuroscientists believe that the Nature paper used chemicals to preserve and stabilize tissue samples of the hippocampus, which could prevent fluorescently-labeled molecules from binding to target cells
.
Gage also suggested that the brain donor's exercise, stress, disease and drug use may all affect the number of new neurons in the hippocampus
.
Image source: pixabay However, in the face of these doubts, the authors of this study are still very confident in the research results
.
One of the authors of the paper, Arturo Alvarez-Villa, believes that "despite the limitations of the study, we have done our best to search comprehensively and carefully, and study many samples of different age groups"
.
The first author of the paper, Shawn Sorrells, responded from a different angle: "Take a step back and think if the adult human brain is really so rare that neural regeneration is so rare that our comprehensive search will If you can't find it, does it really still play an important role in learning and memory?" The answer is still in the air The debate is far from over, and in a recent study published in Neuron, Yale's Jon Jon Arellano, Pasko Rakic and colleagues examined the brains of six cadaveric donors, specifically the dentate gyrus region of the hippocampus
.
One of their targets for this search was doublecortin (DCX) in neurons, which is normally found only in immature neurons
.
The two aforementioned studies, published in Nature, Cell Stem Cell, and a study published in Nature Medicine in 2019 looked for DCX
.
This time Arellano's research team used a more sophisticated method, but found no trace of DCX
.
Human hippocampus slices (Image source: EP Moreno-Jimenez et al.
, 2019) They also further used nuclear RNA to measure the age of neurons, the results were basically consistent with DCX, only 0.
003% of the nuclear RNA showed that they may be newly generated of neurons
.
So Arellano's team is temporarily on the side of "neurons don't regenerate"
.
For papers with the opposite results in the past, Arellano believes that the method used by researchers to identify DCX at that time was problematic and may get "false positive" results, so "this result is not credible"
.
Of course, neuroscientists still question the results of this study
.
Sebastian Jessberg of the University of Zurich in Switzerland believes that it is too early to conclude that adult neurogenesis is extremely rare.
.
"This paper shows a lack of evidence for neurogenesis," he said, "but lack of evidence certainly doesn't mean that neurogenesis doesn't exist
.
We've found a lot of positive evidence for neurogenesis in the human hippocampus
.
If single-nucleus RNA sequencing is considered would be "the only absolute truth", and that would be a scientific misunderstanding
.
" Arellano and Jasberg's statement basically represents the typical views of both parties: "no new neurons can be found" "what has been found is not a newborn neuron" and "not found does not mean that there are no newborn neurons"
.
And what the truth is, we can only wait for further research in the future to give the answer
.
Reading this, how are your brain cells? Cover source: Robina Weermeijer on Unsplash Reference link: https:// d41586-018-02812-6#ref-CR1https://linkinghub.
elsevier.
com/retrieve/pii/S1934590918301218https:// com/neuron/fulltext/S0896-6273(21)00866-7?_returnURL=https%3A%2F%2Flinkinghub.
elsevier.
com%2Fretrieve%2Fpii%2FS0896627321008667%3Fshowall%3Dtrue "Global Science" March new issue sale middle stamp picture Or read the original text to buy it now and click [Watching] to receive our content updates in time
.
Our skin, blood, bones, and many other organs continue to grow new cells throughout our lives
.
However, one organ may be an exception - the brain
.
Author | 27 Reviewer | clefable If you search for "neurons" and "regeneration", you may find some contradictory results, and may even be posted by the same media
.
Take "Universal Science" itself as an example.
In 2018, we reprinted an article entitled "Nature: After Adulthood, Does the Brain Stop Making New Neurons?" ", but less than a month later, we reprinted another article entitled "Refuting Nature! Cell sub-issue: Elderly people can generate "new brain cells".
.
.
" article
.
Is either of these two articles "wrong"? Not so
.
In fact, the question of whether human beings can form new brain neurons in adulthood has been debated passionately for nearly a hundred years, and a unified answer has not been obtained until today
.
Neurogenesis of Neurons In 1928, Santiago Ramón y Cajal, known as the "pioneer of modern neuroscience", declared that the human brain would never form new neurons after adulthood
.
Over the next few decades, this assertion quickly became mainstream thought in academia
.
Until the 1980s and 1990s, many neuroscientists gradually discovered that new neurons can still be formed in the adult rodent and non-human primate brains, a process known as "neurogenesis"
.
In mammals, adult neurogenesis is concentrated in two regions: the hippocampus, which is responsible for learning and memory, and the olfactory bulb, which is responsible for smelling
.
Neurons in the hippocampus (red) | Credit: Thomas Deerinck, NCMIR/SPL 1998 Fred Gage and colleagues at the Salk Institute in Nature Medicine A classic study was published
.
They used a substance called bromodeoxyuridine (BrdU), which is similar to nucleosides and can be taken up by cells when they divide, and is involved in forming the DNA of new cells
.
In this way, BrdU becomes a "tag" for new cells
.
At the time, doctors would use the substance to measure the rate at which cancer cells formed, while Gage and his colleagues wanted to see if neurons were "tagged
.
"
The results directly contradict previous "mainstream thinking": the substance was found in the brains of all five cadaveric donors and was concentrated in the dentate gyrus region of the hippocampus
.
This suggests that the cells here did not divide until after the injection of BrdU—that is, the formation of new neurons in the brain
.
Hippocampus (top) and BrdU-labeled nuclei (bottom arrow) (Image source: PS Eriksson et al.
, 1998) Indeed, more and more scholars have begun to agree with this view, but there are also many scholars who disagree on this Research has raised doubts
.
Some have questioned that Gage et al.
did not examine all neurons, possibly mixing in other regenerative cells
.
In addition, since BrdU injections into humans were quickly banned, there was a lack of evidence to replicate the experiments
.
Although the nuclear explosion is controversial, the 1998 study opened the door to the study of neurogenesis in the human brain, and more and more neuroscientists began to pay attention to this question and try to give their own answers - of course, their answers Also often very different
.
In an interesting study, published in Cell in 2013, Jonas Frisén and colleagues at Karolinska Institutet in Sweden used the nuclear explosions of the 1950s and 1960s.
Residues of experiments to study neurogenesis in the human brain
.
Specifically, Friesen's research ideas are similar to Gage's, and they are all trying to introduce markers to "label" the newborn cells
.
After all, synthesizing DNA is something that almost every cell does before dividing.
As long as these markers are detected in cellular DNA, it means that there are "new cells"
.
This time, Friesen and colleagues used a marker called "nuclear carbon
.
"
Image source: pixabay Nuclear explosion carbon, as the name suggests, comes from nuclear explosion
.
From 1945 to 1963, many countries conducted large-scale surface nuclear explosion tests.
These explosions more than doubled the concentration of the radioactive carbon isotope in the atmosphere - carbon 14, which is called "nuclear explosion carbon"
.
After the nuclear test ban treaty was signed in 1963, the amount of carbon-14 in the atmosphere began to steadily decline due to the dilution effect of the Earth's carbon cycle
.
Today, carbon-14 levels in the atmosphere have largely fallen back to 1950s levels
.
Carbon 14 in the atmosphere enters the human body along the food chain
.
When we divide new cells, these "nuclear explosions" are unknowingly integrated into the newly synthesized DNA and become the "age markers" of the new cells
.
For example, if some cells were formed in 1960, they must have higher carbon-14 content than cells formed in the last two years
.
What Friesen and his colleagues have to do is to use a mass spectrometer to analyze the carbon-14 content of neurons in different areas of the brain, and compare the historical changes in atmospheric carbon-14 concentration to know whether new cells are added to these cells, or even Can be accurate to the year
.
The black line in the figure is the carbon-14 concentration in the atmosphere, the red dot is the carbon-14 concentration in the DNA of non-neuronal cells, and the abscissa is the birth year of the deceased donor
.
In the picture, the carbon-14 concentration in the DNA of the donors born before the large-scale nuclear test was above atmospheric levels, while the DNA of the donors born after the large-scale nuclear test was below the atmospheric level, which means that the measured cells are constantly "renewing" ( Image credit: KL Spalding et al.
, 2013) In Friesen's previous study, carbon-14 levels in all 14 olfactory bulbs examined were largely consistent with the levels of carbon-14 in the atmosphere at the time of the donor's birth
.
That is, the neurons in the olfactory bulb are not "replaced" after birth
.
This time, however, Friesen found that the situation in the hippocampus was completely different
.
The research team looked at the brains of donors of different ages and measured carbon-14 levels in neurons in different regions of the hippocampus
.
To get a more precise understanding of when and how quickly neurons "update", the researchers simulated a number of possible scenarios and compared them with their measurements
.
The results showed that neurons in the dentate gyrus region of the hippocampus of the brain continue to renew even in adulthood
.
Using carbon-14-labeled cell ages, the researchers compared the proportion of "renewal" neurons in donors by birth date, and roughly estimated that we generate about 1,400 new neurons per day
.
The black line in the figure is the atmospheric carbon-14 concentration, and the blue point is the carbon-14 concentration of the neuronal DNA in the dentate gyrus region of the hippocampus, showing a trend similar to that of non-neuronal cell DNA (Image source: KL Spalding et al.
, 2013 ) Contradictory Research Yet the story is not over
.
As mentioned before, research on whether brain neurons can regenerate is endless, and the academic community basically agrees on the olfactory bulb (that is, the olfactory bulb cannot generate new neurons in adulthood), but the controversy about the hippocampus has continued
.
The two articles we mentioned at the beginning are a good example
.
In March 2018, a study published in Nature used fluorescent markers to label possible "new cells" and took a closer look at cell morphology, but did not find any neurons in a "young" state
.
However, less than a month later, Cell Stem Cell published an article with the exact opposite result
.
For the first time, the researchers looked at neurons in the hippocampus shortly after an individual's death, also stained with fluorescent markers, and thought they had found large numbers of immature neuronal and interneuron progenitors
.
Some neuroscientists believe that the Nature paper used chemicals to preserve and stabilize tissue samples of the hippocampus, which could prevent fluorescently-labeled molecules from binding to target cells
.
Gage also suggested that the brain donor's exercise, stress, disease and drug use may all affect the number of new neurons in the hippocampus
.
Image source: pixabay However, in the face of these doubts, the authors of this study are still very confident in the research results
.
One of the authors of the paper, Arturo Alvarez-Villa, believes that "despite the limitations of the study, we have done our best to search comprehensively and carefully, and study many samples of different age groups"
.
The first author of the paper, Shawn Sorrells, responded from a different angle: "Take a step back and think if the adult human brain is really so rare that neural regeneration is so rare that our comprehensive search will If you can't find it, does it really still play an important role in learning and memory?" The answer is still in the air The debate is far from over, and in a recent study published in Neuron, Yale's Jon Jon Arellano, Pasko Rakic and colleagues examined the brains of six cadaveric donors, specifically the dentate gyrus region of the hippocampus
.
One of their targets for this search was doublecortin (DCX) in neurons, which is normally found only in immature neurons
.
The two aforementioned studies, published in Nature, Cell Stem Cell, and a study published in Nature Medicine in 2019 looked for DCX
.
This time Arellano's research team used a more sophisticated method, but found no trace of DCX
.
Human hippocampus slices (Image source: EP Moreno-Jimenez et al.
, 2019) They also further used nuclear RNA to measure the age of neurons, the results were basically consistent with DCX, only 0.
003% of the nuclear RNA showed that they may be newly generated of neurons
.
So Arellano's team is temporarily on the side of "neurons don't regenerate"
.
For papers with the opposite results in the past, Arellano believes that the method used by researchers to identify DCX at that time was problematic and may get "false positive" results, so "this result is not credible"
.
Of course, neuroscientists still question the results of this study
.
Sebastian Jessberg of the University of Zurich in Switzerland believes that it is too early to conclude that adult neurogenesis is extremely rare.
.
"This paper shows a lack of evidence for neurogenesis," he said, "but lack of evidence certainly doesn't mean that neurogenesis doesn't exist
.
We've found a lot of positive evidence for neurogenesis in the human hippocampus
.
If single-nucleus RNA sequencing is considered would be "the only absolute truth", and that would be a scientific misunderstanding
.
" Arellano and Jasberg's statement basically represents the typical views of both parties: "no new neurons can be found" "what has been found is not a newborn neuron" and "not found does not mean that there are no newborn neurons"
.
And what the truth is, we can only wait for further research in the future to give the answer
.
Reading this, how are your brain cells? Cover source: Robina Weermeijer on Unsplash Reference link: https:// d41586-018-02812-6#ref-CR1https://linkinghub.
elsevier.
com/retrieve/pii/S1934590918301218https:// com/neuron/fulltext/S0896-6273(21)00866-7?_returnURL=https%3A%2F%2Flinkinghub.
elsevier.
com%2Fretrieve%2Fpii%2FS0896627321008667%3Fshowall%3Dtrue "Global Science" March new issue sale middle stamp picture Or read the original text to buy it now and click [Watching] to receive our content updates in time
