Adult neurogenesis

Adult neurogenesis is the idea that humans continue to produce new neurons into adulthood. Neurons are the specialized cells in the brain that send and receive messages as part of the central nervous system. Humans are born with an estimated one hundred billion neurons. For many years, it was believed that neurons did not regenerate as other cells in the body do. Scientists thought that once neurons died they could not be replaced.

Research in the late twentieth and early twenty-first centuries has called this idea into question. Scientists are still uncertain whether adult neurogenesis is actually possible in humans, although there have been studies proving that it does occur in other types of mammals, such as rats. If adult neurogenesis is possible and scientists could understand what spurs the production of new neurons, then they might be able to use this information to treat brain injuries or disorders, such as Alzheimer’s disease.

Background

Two main types of cells are present in the brain: neurons, which receive and transmit messages, and glial cells, which provide support for neurons and have several important jobs, such as regulating blood flow in the brain and clearing away dead cells.

Neurons and glia form from neural precursor cells, also known as neural stem cells (NSCs). Stem cells are undifferentiated cells that have the potential to develop into a specialized cell of the body, such as a neuron. During the brain’s development, the NSCs divide into two. This action may produce two new stem cells, or it could produce what are called early progenitor cells. These early progenitor cells will produce either more of themselves or become the specialized cells of the brain, neurons and glia.

Neurons then migrate to the parts of the brain where they will perform their work so they can continue to specialize, or differentiate. There is still much that scientists do not understand about neurons. What they do know has only been discovered in about the last one hundred years.

Early in the twentieth century, a Spanish scientist named Santiago Ramón y Cajal discovered that neurons were the building blocks of the brain. For this discovery, he received the Nobel Prize in 1906. During Cajal’s time, scientists believed that people were born with most of the neurons that they would ever have. They thought that some neuron development continued after birth to assist in building important neuropathways in the brain. However, they did not think that neurons could regenerate as other cells in the body, such as skin cells, could. Once neurons were damaged or destroyed, scientists believed they were gone forever and new neurons would not take their place.

Research into the possibility of adult neurogenesis began in the 1960s. In 1962, American scientist Joseph Altman was working at the Massachusetts Institute of Technology (MIT). There, he found evidence of new neurons in the brains of adult rats. This neurogenesis was specific to certain regions of the brain. One was the seahorse-shaped hippocampus, which is an area of the brain tied to memory. Later, Altman also found evidence of new neurons in the olfactory bulb, a structure in the forebrain related to the sense of smell.

Many scientists, although curious about the idea of adult neurogenesis, did not believe that Altman’s research proved that the process was actually possible in humans. Eventually, the refusal of the scientific community to take his work seriously led to Altman leaving the field of neurogenesis behind. Nevertheless, additional research by other scientists continued.

In the late 1970s, fellow scientist Michael Kaplan confirmed Altman’s research regarding neurogenesis in the brains of adult rats. Like Altman, Kaplan too would grow frustrated with the scientific community’s unwillingness to consider the possibility of adult neurogenesis and move on to other projects. In the 1980s, scientists Fernando Nottebohm and Steve Goldman studied neurogenesis in the brains of adult male canaries. They found that the canaries would experience an increase in neurons during the spring when they learned new songs to attract female mates.

While Nottebohm and Goldman’s research was compelling, some scientists still argued that this generation of new neurons might not be possible in primates. One of these scientists was Pasko Rakic. Rakic studied the brains of twelve rhesus monkeys, using the same process Altman used on his rats. Unlike Altman, Rakic did not find any evidence that adult primates produced new neurons. In his 1985 paper, “Limits of Neurogenesis in Primates,” Rakic concluded that conventional scientific thinking about neurons was correct—primates are born with almost all the neurons they will ever have and neuron production does not continue into adulthood.

Still, more scientists were curious about the possibility of adult neurogenesis. One was Elizabeth Gould, who discovered the work of Altman and Kaplan after she was doing her own experiments with rat brains in the late 1980s. At first, Gould believed she was miscounting the number of neurons in the samples of rat brains she was examining. Then, she wondered if maybe she was finding new neurons after reading the work of Altman and Kaplan. Gould began studying the brains of adult marmosets and found that these primates created new neurons in the olfactory cortex and the hippocampus.

In 1998, scientists Fred Gage and Peter Eriksson studied the brains of human cancer patients who had been injected with a marker chemical called bromodeoxyuridine (BrdU). This marker was then incorporated into the deoxyribonucleic acid (DNA) of these patients’ dividing cells to see how the cancer cells in the body grew. Gage, Eriksson, and their teams examined these patients’ brains after they died. If new neurons were not forming, then the scientists would not find evidence of the BrdU in the brain. However, they did find BrdU-marked neurons in part of the hippocampus. They published their findings in a paper called “Neurogenesis in the Adult Human Hippocampus” in the November 1998 edition of the journal Nature Medicine.

Overview

Since the late 1990s and early 2000s, research into adult neurogenesis and its potential applications has increased dramatically. A 2013 study using carbon dating seemed to confirm Gage and Eriksson’s 1998 findings about adult neuron production in the hippocampus, suggesting that humans replace hundreds of neurons every day. Other studies conducted in the 2010s even suggested that certain behaviors, such as engaging in extended aerobic exercise several times a week and avoiding stress, could affect the number of new neurons produced in the brain.

Still, the idea that the brain was producing new neurons on a daily basis did not seem correct to some scientists. In early 2018, a study led by Arturo Alvarez-Buylla at the University of California, San Francisco, was published in Nature. The scientists on Alvarez-Buylla’s team countered the twenty-year-old claims of Gage and Eriksson in a study that examined brain tissue from fifty-nine people, ranging in age from prenatal to seventy-seven. Some of the samples were obtained during brain surgery, while others were obtained postmortem. The scientists in Alvarez-Buylla’s study found that neuron production drops off to almost zero after age seven. The team argued that the evidence of neurogenesis in adult brain samples previously found by scientists like Gage and others may have actually been glial cells rather than neurons.

Just a month after Alvarez-Buylla’s study was published, another study on neurogenesis in adults was printed in the journal Cell Stem Cell. Maura Boldrini and fellow researchers at Columbia University studied brain samples from twenty-eight people aged fourteen to seventy-nine. The scientists examined the entire hippocampus instead of just one particular section. They used immunofluorescence (which uses florescent dyes to allow scientists to see certain cells and molecules) and immunocytochemistry (which can confirm the location of certain peptides or proteins using antibodies that bind to these molecules) to track the different stages of neural development they were observing. Then, the scientists used a process called stereology, which uses a computer algorithm, to calculate the total cells in each region. Boldrini’s team found thousands of young neurons in the area of the hippocampus where other scientists had observed their presence previously.

Although there is no consensus as of yet on whether adult neurogenesis actually occurs in humans, the process has potential implications for a number of medical conditions and diseases. If neurons do continue to form into adulthood, understanding their growth and trying to direct that growth could lead to breakthroughs in treating degenerative brain disorders such as Alzheimer’s disease. Additionally, it might be possible that understanding the regeneration of neurons in adult brains could treat mood disorders such as depression. It might also help scientists understand how to help the brain recover after a traumatic injury.

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