Adults may be unable to grow new neurons in the brain 鈥� contrary to previous findings.
The question of whether adults can form new neurons, called neurogenesis, has long been a source of controversy. While researchers have discovered adult neurogenesis in and , any evidence of this ability in humans is less clear.
The hippocampus, which has been linked with adult neurogenesis, is vulnerable to Alzheimer鈥檚 disease and other neurodegenerative conditions. This has led to arguments that adult neurogenesis may hold the key to treating these conditions.
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and at Yale University and their colleagues examined the brains of six people, with an average age of 53, who had donated the organ to science. They also studied the brains of seven macaques and 18 pigs, and looked at data from studies of mouse brains.
鈥淭here are two regions where neurogenesis occurs [in non-human animals],鈥� says Arellano. 鈥淥ne is the olfactory bulb and the other is the hippocampus.鈥�
The human olfactory bulb, which is important for our sense of smell, is already considered to be incapable of adult neurogenesis, says Arellano, but there is still debate when it comes to the hippocampus.
The researchers used a technique called single-nucleus RNA sequencing to study the hippocampal cells in the brain samples. This method targets the nuclear RNA molecules that can help turn DNA code into proteins and can characterise the cell 鈥� which can help establish its age.
鈥淵ou basically go to the cell, break the membrane of the cell and get the RNA that is inside the cell,鈥� says Arellano. 鈥淚t can give us information like 30 different genes in that cell which helps us better classify it.鈥�
鈥淚t鈥檚 like comparing a single photograph of a person to lots of pictures of them,鈥� he says. 鈥淚f you have 100 pictures of that person in different moments over the day, you have a much better idea of how that person looks.鈥�
The researchers focused on neurons in part of the hippocampus called the dentate gyrus, where adult neurogenesis in mammals has . However, they found that just 0.003 per cent of their human sample cells had a nuclear RNA profile that suggested they were newly created neurons.
For comparison, about 6.6 per cent of the cells in the dentate gyrus of mice could be new neurons, while 2 per cent of the macaques鈥� cells in this brain region showed signs of being new neurons.
The researchers also looked in their brain samples for DCX, a protein marker for newly formed neurons. 鈥淒CX has been shown to be a very specific marker for neurons that are not mature,鈥� says Arellano.
DCX had been found in the human adult dentate gyrus by other researchers, leading to arguments that adult neurogenesis is real. But Arellano argues these findings could be explained by the method the researchers used to identify DCX, which has the potential to lead to false identifications. 鈥淵ou cannot trust it,鈥� he says.
Using a more fine-tuned method, the researchers didn鈥檛 find any DCX protein in the human dentate gyrus. Combined with the nuclear RNA data, this suggests to them that adult neurogenesis doesn鈥檛 exist.
Rakic says it is more impressive that humans lack such neurogenesis.聽鈥淚鈥檓 over 88 years old and I have billions of neurons that have lasted a lifetime,鈥� he says. 鈥淭hat鈥檚 more impressive to me than the idea that mice can make new neurons. Everything that I鈥檝e learned is still there in my brain 鈥� fish don鈥檛 have that.鈥�
鈥淭his is an important new paper,鈥� says at the University of California, San Francisco. 鈥淚t is consistent with previous studies which support the conclusion that if adult neurogenesis continues, it is a very rare phenomenon,鈥� he says.
But at the University of Zurich in Switzerland thinks it is too soon to conclude that adult neurogenesis is vanishingly rare. 鈥淭he paper now shows absence of evidence 鈥� using their approach for single-cell isolation and data analyses,鈥� he says. 鈥淏ut that absence of evidence certainly is not proof for the absence of neurogenesis. There is a large body of positive evidence for neurogenesis in the human hippocampus. It would be a scientific misunderstanding to believe that single nucleus RNA sequencing 鈥� only detecting a fraction of all genes expressed within a cell 鈥� would be 鈥榯he single absolute truth鈥�.鈥�
鈥淭he significance of neurogenesis is that, if it exists, it adds a level of plasticity to the brain that may be important to understand how the hippocampus works and encodes information,鈥� says Jessberger. 鈥淭argeting such precursors or their daughter cells may be used to harness the regenerative potential of the brain.鈥�
Neuron
