The term neurogenesis is made up of the words “neuro” meaning “relating to nerves” and “genesis” meaning the formation of something. The term therefore refers to the growth and development of neurons. This process is most active while a baby is developing in the womb and is responsible for the production of the brain’s neurons.
The development of new neurons continues during adulthood in two regions of the brain. Neurogenesis takes place in the subventricular zone (SVZ) that forms the lining of the lateral ventricles and the subgranular zone that forms part of the dentate gyrus of the hippocampus area. The SVZ is the site where neuroblasts are formed, which migrate via the rostral migratory stream to the olfactory bulb. Many of these neuroblasts die shortly after they are generated. However, some go on to be functional in the tissue of the brain.
Previously, neuroanatomists such as Santiago Ramon Cajal believed the nervous system was a fixed system that was not capable of regeneration and that neurogenesis in humans and other animals no longer continued after the embryonic development phase. However, in the second half of the 20th century, researchers discovered that neurons do continue to form throughout life.
In 1962, the first evidence of adult neurogenesis was demonstrated by Joseph Altman who also identified the rostral migratory stream in 1969. In animal studies performed throughout the 1960s, Altman injected adult rats with a radioactive label that gets incorporated into any newly forming DNA strands so that newly forming cells can be detected. Analysis of the rat brains showed that the cells the radioactive molecule had flagged up as newly formed in the brain were in fact neurons. Altman’s studies showed that the formation of neurons in the adult rat seemed to be limited to certain areas of the brain, one of which was the hippocampus, which is now known to play a crucial role in learning and memory.
These findings were largely ignored by the scientific community since the radioactive label was not specific to neurons and the imaging techniques used could not discern between nerve cells and other cell types. Furthermore, the conventional thinking was that the brain was made up a fixed network of neurons that formed a circuit and people assumed that the ongoing incorporation of new cells into this circuit would disrupt the brain’s ability to learn and remember.
More substantial evidence for neurogenesis during adulthood was provided by Fernando Nottebohm in the 1980s. He also used the radioactive molecule that Altman used to show the formation of new cells in the brains of birds. However, he also discovered that the newly formed cells could conduct electricity, which demonstrated that they had to be nerve cells.
Although this and other studies had pointed towards the existence of adult neurogenesis, the concept was not taken more seriously until the early 1990s when more advanced technologies became available. For example, scientists discovered stem cells in the brains of adult mice and that these precursor cells could differentiate into nerve cells. In addition, new labeling and imaging techniques were developed that helped scientists to prove that new cells do form in the adult brain and that in some cases, those cells were neurons.
In 1996, rat studies showed that although neurogenesis does significantly slow down as a person ages, it never completely ceases and in 1998, scientists finally managed to provide evidence that neurogenesis does occur in the brains of adult humans.
This new understanding that adult neurogenesis both takes place and forms functional neurons led scientists to wonder what role the process plays in cognition, what its effects are on cognitive health and whether the process could be altered to improve cognitive health as humans age.
In 2005, researchers found that exercise had significant positive effects on neurogenesis. In a study of older mice, mice that ran on a wheel were found to have enhanced neurogenesis compared with sedentary mice. The mice that exercised also completed a spatial learning task to the same standard as younger mice.
In 2009, a study showed why adult brain neurogenesis may be needed. One location where neurogenesis takes place is in a region of the hippocampus referred to as the dentate gyrus, which is vital in allowing the brain to differentiate between similar memories such as where a person has placed their car keys one day as opposed to the day before. When researchers inhibited neurogenesis in mice, they found the mice were less able to remember parts of a maze that were similar.
A landmark study in 2013 created a model of cell turnover in the hippocampus over the human lifespan based on estimates of neuronal aging in the hippocampus of post-mortem brain samples. The study showed significant neurogenesis took place in this brain region, suggesting the process is a big contributor to brain function.
Since 1962, when Altman first attempted to provide evidence for neurogenesis in adults, the development of more sophisticated tools and technologies has enabled scientists to better understand this process and make discoveries about its impact on cognitive health and the aging brain; discoveries that researchers will continue to build on to establish strategies that may help to prevent cognitive decline in the future.
Edited by Sally Robertson, BSc