Biology 202
2000 First Web Report
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Neurogenesis in the Human Brain:

Fact or Fiction?

Stephanie Wall

Imagine a world where scientists could implant new brain cells into areas of the brain that are damaged by disease or accidents. Imagine replacing brain cells lost to aging, or even enhancing areas of the normal brain. Recent newspaper headlines, such as "A Decade of Discovery Yields a Shock About the Brain" (1) and "Brain May Grow New Cells Daily" (2) have indicated such advances may be in the near future. How far-fetched are such claims?

In the past several years, evidence has emerged that challenges the longstanding belief that humans are born with all the brain cells, or neurons, they will ever have. Recent experiments on monkeys have shown that new neurons are continually added to the cerebral cortex throughout adulthood. Some believe that this finding will prove to be true in the human adult brain as well. One scientist compared such a change in view to a paradigm shift, described by Thomas Kuhn as occurring when one major scientific theory is replaced by another. (3) In this paper I examine recent research on neurogenesis in the brain and attempt to answer the question of whether such conclusions are merited. And I ask what would be the implications if the adult human brain could regenerate itself.

The neuron is the basic building block of the human brain and nervous system. Each of the more than ten billion neurons in the brain receives, processes and transmits electrical information from one part of the body to another. A neuron consists of a cell body and two or more extensions, called dendrites and axons, which may be as long as one meter in humans. (4) Dendrites receive inputs and conduct signals toward the cell body, whereas axons conduct signals away from the body where they make connections with other neurons or target cells. These signals convey information that allows a person to interact with his or her environment - from breathing, to thinking, to sneezing.

Our current understanding of the brain is that the adult human brain's neurons are static in number. Unlike cells in most tissues, which are generated and replaced throughout life, most neurons of the mammalian brain are entirely generated during early development are not replaced if lost. (5) This view of human brain development is based in part on experiments on macaque monkeys conducted in the 1960's by Dr. Pasko Rakic, a neuroscientist at Yale University. These studies showed that brains develop as dendrites and synapses grow around a fixed number of neurons after birth. (1) The brain continues to form new synapses between pre-existing components. However, it has appeared that a person is born with a fixed allotment of neurons which invariably declines with age. The fact that many people do not recover the ability to speak or walk after strokes or other brain injury also seems to support the view that adult brains do not add new cells.

New evidence began to emerge in 1965 when scientists reported that new neurons are generated in the dentate gyrus of the hippocampus of the adult rat brain. The hippocampus is a brain structure that is important for memory function. (6) Evidence has accumulated that neurogenesis occurs in the adult dentate gyrus in other mammals, including tree shrews and marmoset monkeys (7), (8). In 1998, a study was undertaken to investigate whether neurogenesis occurs in the adult human brain. Human brain tissue was obtained postmortem from patients who had been treated with a radioactive marker that labels the DNA of dividing cells. (9) New neurons, identified by these markers, were found in the dentate gyrus of these patients. The results indicate that the human hippocampus retains its ability to generate neurons throughout life. (10) And in May 1999, researchers reported evidence for the production of new neurons in the hippocampal dentate gyrus of adult macaque monkeys. Macaque monkeys are phylogenetically close to humans; both species are Old World primates and have similar hippocampal structure and function. (5)

But what about neorogenesis in other, higher processing centers of the brain? The cerebral cortex, or neocortex, is the largest and most complex part of the human brain, accounting for some of the most sophisticated human behavior. In October 1999, a study by Elizabeth Gould, et. al., was published that investigated neurogenesis in the adult primate neocortex. (11) The researchers reported that in adult macaque monkeys, new neurons are added to three neocortical association areas that are important in cognitive function: the prefrontal, inferior temporal and posterior parietal cortex. No neurons were detected in a fourth area, the striate cortex, a primary sensory area that processes visual information from the eyes. The new neurons appeared to originate in the subventricular zone, where the stem cells that give rise to other cell types are located, and to migrate through the white matter to the neocortex, where they extend axons.

The authors concluded by saying, "The presence of new neurons in brain areas involving learning and memory supports earlier suggestions that adult-generated neurons may play a role in these functions." (11) They also made an intriguing suggestion: that the regeneration of new neurons in the neocortex throughout adulthood provides a "continuum of neurons of different ages that may form a basis for marking the temporal dimension of memory." (11) The researchers plan to test this hypothesis by blocking the formation of new neurons in monkeys' brains. If deficits in memory and learning appear in the monkeys' behavior, this may be evidence that the new neurons have a role in memory and learning. (2)

What do these data mean? First, the data are a lesson in the scientific process. Science is less about the discovery of facts and more about making observations and testing hypotheses through experiment. The theory that neurogenesis in the adult primate brain occurs only during development is challenged by new experimental evidence that does not support this theory. For a new theory to be widely accepted, however, it must be supported by a large body of evidence. While the preponderance of evidence shows that neurons are likely regenerated in the brains of adult primates, evidence is still sparse that adult neurogenesis in humans occurs. To answer questions about neorogenesis in the adult human brain, scientists require a nonhuman primate as phylogenetically close to humans as possible. The macaque monkey has proven to be an appropriate model, but more study is needed.

Second, the data show that scientific claims made in popular media may be misleading and are, by their nature, incomplete. The "shock" in the headline "A Decade of Discovery Yields a Shock About the Brain" (2) implies a sudden, single event that has taken the scientific community by surprise. As the chronology of evidence shows, the recent study by Dr. Gould and her colleagues is the latest in a long and multi-branched line of experiments about neurogenesis in the brain. Studies such as Dr. Gould's must be evaluated in the context of the larger whole. Indeed, the study of neurogenesis is one part of the larger, ongoing inquiry into how the brain works.

Finally, what are the implications of this new evidence? The finding that the adult human brain regenerates its cells suggests new therapies for repairing the aged or damaged brain. Degenerative brain diseases, such as Parkinson's, are defined by the loss of neurons. It may be possible to use the brain's own restorative potential to treat such brain diseases. The treatment of human brain disorders that involve the hippocampus, including epilepsy and schizophrenia, may be added by the ongoing neurogenesis in the dentate gyrus of affected patients. (5) In addition, this finding may lead to a new understanding of hippocampal learning and memory.

However, the demonstration of adult neurogenesis in humans raises many more questions than answers. Where did these new neurons originate, how many are there, and what happens to them? Do these new neurons cumulatively add to the population of older cells, or do they replace older neurons with no net increase in cell number? How many of these neurons extend axons, receive synaptic input, and produce action potentials? Scientists face the challenge of further hypothesizing and testing answers to these questions. Society faces the challenge of maintaining a healthy skepticism and critically evaluating those answers.

WWW Sources

1)Blakeslee, Sandra. "Decade of Discovery Yields a Shock About the Brain." New York Times, January 4, 2000.

2) Wade, Nicholas. "Brain May Grow New Cells Daily" New York Times, October 15, 1999.

3)Kuhn, Thomas. Philosopher of science.

4)A Neuron

5) Kornack, D. and P. Rakic. "Continuatoin of neurogenesis in the hippocampus of the adult macaque monkey." Proceedings of the National Academy of Sciences, May 11, 1999.

6)The Hippocampus

7)Gould, E., et. al. "Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation." The Journal of Neuroscience. April 1, 1997.

8)Gould, E., et. al. "Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress." Proceedings of the National Academy of Sciences. March 17, 1998.

9)DNA Methods/Autoradiography

10)Eriksson, PS., "Neurogenesis in the adult human hippocampus." Nat Med. Novemeber 4, 1998.

11)Gould, E., "Neurogenesis in the Neocortex of Adult Primates." Science. October 15, 1999.

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