Researchers revolutionise previous brain research
The human brain can produce new nerve cells even in adults, in a small part of the brain called the hippocampus. By delivering proof for this thesis, researchers have answered one of the most important questions in neuroscience. Dr. Hagen Huttner, neurologist at the Department of Neurology, Universitätsklinikum Erlangen, was part of a team of – mainly Swedish – researchers that used a side effect of the more than 500 above ground nuclear bomb tests carried out during the Cold War to provide the sought-after evidence: during these nuclear tests, a large amount of a radioactive carbon isotope was released into the atmosphere. The researchers’ findings have recently been published in the journal ‘Cell’.*
‘For decades science was ruled by the dogma that the adult human brain doesn’t produce new neurons,’ Hagen Huttner explains. The only indicator so far that there is a small area of the brain that continues to undergo neurogenesis – namely the hippocampus, which is involved in mnemonic and learning processes – was provided by Swedish researchers in 1998, using the brains of five patients who died from tongue cancer. However, since the substance that was used to prove nerve cell division turned out to be toxic, the findings could never be reproduced and confirmed in humans. Since then, top research papers have been published that have only been able to confirm hippocampal neurogenesis in rodents.
The team of researchers, co-ordinated by the Karolinska Institute in Stockholm, examined the cellular regeneration of the human hippocampus using a unique method: they dated cells with a procedure based on the release of carbon during nuclear bomb tests. ‘This radiocarbon dating is not really new. Archaeologists use it regularly to date their finds, for instance,’ Hagen Huttner explains. ‘However, for millennia, the ratio of normal to radioactive carbon was relatively constant, meaning that the accuracy of the dating method was not optimal. But the nuclear bomb tests changed this carbon ratio dramatically and it is now slowly returning to normal after nuclear test ban treaties have been implemented. This means that the temporal resolution of radiocarbon dating has become fantastically accurate and we can use it for scientific experiments on hippocampal neurogenesis.’
Radiocarbon dating of nerve cells makes use of the fact that the radioactive carbon was absorbed into humans via plants and animals in the food chain and was incorporated into the DNA of every new cell at exactly the same ratio to normal carbon as the atmospheric value during the year of the cell’s ‘birth’. If one isolates the DNA of nerve cells that do not divide after their birth and examines them with regard to the ratio of normal to radioactive carbon, the birth year of the cell can be determined with great accuracy.
The researchers were able to prove that a large subpopulation of hippocampal nerve cells, approximately a third, is newly generated throughout life. Huttner: ‘In an adult human, this corresponds to roughly 1400 nerve cells that are renewed daily. In other words: every year, about two percent of the group of regenerating nerve cells within the hippocampus are regenerated, and this rate of regeneration decreases only marginally with age.’ The extent of neurogenesis seems great and yet it also seems very little considering the billions of neurons in the entire brain.
Another core question, namely to what extent neurogenesis is actually important to humans and human brain function, remains unanswered. ‘The hippocampus is a very old brain structure, evolutionarily speaking. However, the important higher cognitive functions in humans that distinguish us from non-human animals are located in the cortex. Using radiocarbon dating, it was possible to show that no neurogenesis occurs here in a healthy adult. It is now intriguing to examine whether neurological disorders that affect the cortex could trigger neurogenesis here too – this would make the topic of neurogenesis interesting from a physician’s point of view as well,’ says Huttner. Using radiocarbon dating, Huttner and colleagues are now researching whether neurogenesis occurs in the human cortex after a stroke.
*Kirsty L. Spalding K.L., Bergmann O., Alkass K., Bernard S., Salehpour M., Huttner H.B., Boström E., Westerlund I., Buchholz B., Possnert G., Mash D., Druid H., Frisén J.: „Dynamics of hippocampal neurogenesis in adult humans“, Cell, Volume 153, Issue 6, 1219-1227, 6 June 2013. Doi: 10.1016/j.cell.2013.05.002
Dr. med. Hagen B. Huttner
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