The history of the study of neurogenesis

by Jonathan Lee (’22) | March 29, 2021

Art by Allyson Wang (’23)

Manifesting every action, experience, feeling, memory, and thought, the brain is the most complex organ in the human body. This compact and wrinkly gelatinous ball contains eighty-six billion neurons. Through structures called synapses, a single neuron can make up to tens of thousands of connections, interchanging connectivity to form memories. Our brains are so complex because each second, neurons make millions of connections that constantly change in strength as well as pattern. Until the 1960s, the predominant theory on neural cell growth was that it did not occur after the brain finished development, as scientists believed that neurons—which make up most of the adult brain—could not divide and proliferate. However, this theory that neurons don’t grow back when destroyed was about to change forever. 

In 1960, Joseph Altman was the first neurobiologist to discover neural cell development in the adult rodent cerebrum (the largest part of the brain). His intuition that the neurons could proliferate using neural stem cells led to several experiments. Altman used radioactive thymidine—a nucleoside designed to integrate into the DNA of dividing cells—as an indicator of new cell birth. Through the injection of this nucleoside into rodent brain cells, he was able to tag the areas of integration. He discovered that the label was most present in two regions: the olfactory bulbs and the dentate gyrus of the hippocampus. The olfactory bulbs are in charge of the sense of smell, while the dentate gyrus is responsible for memory formation. This indicated that the adult brain continuously adds details to already constructed memories, incorporating scent into these episodic memories. 

Altman’s research planted a seed of doubt about the widely accepted belief that no new cell growth could occur in the adult brain. After thirty years of dispute and contradictory studies, in 1992, Rusty Gage—who is now 70 and president of the Salk Institute for Biological Sciences in San Diego—confirmed the results of Altman’s studies using a more precise molecule and testing it in humans, rather than rodents. The molecule the Salk Institute used, bromodeoxyuridine, was designed to target neural cells, adding a level of specificity that eliminated the implausibility and deniability of previous experiments. 

However, it didn’t just stop there. A Princeton lab used the results of Gage’s experiment to study how stress could decrease the number of new neurons created, prompting Gage’s lab to study what could encourage further neuron growth. While the Princeton lab studied the impacts of predator scent, Gage’s lab began to study and evaluate the impacts of the environment as well as lifestyle on neurogenesis in adult rodents. They compared the results of a habitat with added stimulants and exercising equipment to a normal environment. Gage’s lab soon realized that environmental enrichment increased the volume of the brain to such a clearly observable extent that there was no need for advanced methodology. 

Since then, Gage has transitioned the application from rodents to humans, similar to what he did thirty years prior with the original experiment. The study showed that exercise was an enriching activity that could give rise to new populations of neurons. As an active runner his entire life, the conclusion that he came to was a relief on many levels. With increased stimulation through activities such as running, the brain replicated cells much faster in the region involving memory, which could be a possible incentive for adults to find time to exercise. 

Although the advancement of this field of research is impressive given the time frame, there is still a lot left to unearth. Gage’s research is only the beginning of endless applications to prevent our brains’ deterioration, possibly providing insight into the treatment and prevention of dementia. I, for one, eagerly await more discoveries on the horizon in this rapidly changing field.

Categories: Science

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