By: Gregory Brown, MD/PhD student
Whether or not your brain can form new neurons (the cells that form the wiring of the brain) has perplexed the neuroscience community for decades. If the brain can regenerate, this could have important implications in restoring brain health. However, the debate is quite contentious.
Side 1: Neurogenesis does occur in the hippocampus
Neurogenesis (forming new neurons) in the hippocampus, the memory center of the brain, has been identified in other species. But does it occur in humans?
Science recognizes that new brain cells form shortly after birth, but the scientific community has believed for years that they do not form in adulthood.
Eriksson et al. investigated if neurogenesis also occurs in the hippocampus of the adult human brain. To do this they used an interesting technique.
A marker known as bromoeoxyuridine (BrdU) labels DNA during the part of the cell cycle when DNA is being synthesized. Since, DNA would be synthesized when a cell divides, this enables scientists to identify the generation of new neurons.
A BrdU labeled cell is a new cell.
Notably, this technique would also stain neurons that are repairing their DNA.
Subjects were given BrdU as part of cancer treatment (cancer cells rapidly divide). The authors then looked at their brains after they passed away. The authors were able to identify new cells in the dentate gurus (DG), which is part of the hippocampus. Quantification of these cells revealed approximately 100 BrdU-labeled cells per mm3.
The findings also revealed a decrease in labeled cells over time from labeling. This may indicate a progressive neurodegeneration; however, there is only one patient per time point, so conclusions are flimsy.
Another interesting finding from this quantification is the patient who died 18 days after labeling at age 72, the oldest age of death had the highest or second highest number of cells per region. This could indicate new cells late into life, and pretty constant, rapid neurogenesis.
These findings alone are not indicative of neurogenesis, as the new cells may be glial cells (another type of brian cell, that is involved in neuronal support). Using co-localization by staining for a neuronal marker, NeuN, the authors were able to identify that some of the BrdU stained neurons did express NeuN.
Other staining techniques identified that approximately 20% of the cells were neurons [neurons produce calbindin and neuron specific enolase (NSE)]. These finding are groundbreaking support that human adult neurogenesis can occur.
Side 2: Neurogenesis does not occur in the hippocampus
Another point of view is that human neurogenesis occurs primarily in childhood and not in adulthood. Research by Sorrels et al. argues this point using a defined set of cells that eventually divide and become neurons (called neural progenitor cells).
The authors identified many dividing neural progenitors, which express the genes Ki-67 and SOX1/2, in the fetal dentate gyrus at 14 weeks gestation. By age 7, these progenitor cells were mostly depleted. The authors also investigated young neurons in the dentate gyrus.
The findings indicate that the number of young neurons declines greatly over the first few months of life and become undetectable after 13 years.
Overall, these finding support the claim that human neurogenesis in the hippocampus rapidly declines after birth and minimally occurs in adulthood.
Verdict
The competing viewpoints highlight the lack of clarity which often surrounds recent scientific queries. Both findings are methodologically very sound, and unfortunately, obtaining the truth is limited by current scientific tools and ethically probing deep brain structures throughout life.
We cannot cut open a living person’s brain to just look at their brain.
Eriksson et al. is limited by the sample size, but the work takes advantage of patients undergoing treatment for another disease, which just happens to provide a method to investigate neurogenesis. The creativity is impressive, and the use of multiple neuronal markers, as well as the well know glial marker GFAP to identify non-neuronal types, lends credibility to the findings.
Sorrels et al. also took advantage of another pathology, epilepsy, to be able to study the brains at various time points of life. And these authors use a more advanced genetic approach.
Despite the debate whether neurogenesis occurs, whether or not a clinically significant amount occurs is also important. Is one new cell going to make a difference in brain function? Perhaps we could hack the neurogenesis process, but uncontrolled cell growth sounds a lot like cancer. As of now, the idea of new neurons seems clinical unimportant.