© 2018 by Janelle E. Letzen, PhD

 
Neuron Life Cycle
What do we know about the lifecycle of neurons?

In June 1998, a research article was published that stated, “It is likely that humans are born with all of the nerve cells (neurons) that will serve them throughout life," which was a fairly widespread belief among scientists at the time. Only months later, another group of scientists provided evidence against this belief by showing the ability of brain cells to actually grow in human adults. Twenty years later, what do we now know about the life cycle of our neurons?

 

Let’s start at the beginning with the birth of a cell, or neurogenesis, which seems to involve cells called “stem cells.”

What are stem cells?

Stem cells are found naturally in humans. But, whereas cells like neurons have specialized functions and are often unable of renewing themselves, stem cells are unique because they: 1) are unspecialized cells that can regenerate themselves, and 2) can be experimentally changed to function just like specific organ and tissue cells. For these reasons, ongoing research is looking at how stem cells can be used in clinical therapies. 

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Types of Stem Cells

Starting around the 1980s, stem cell experiments used two types of cells, called embryonic stem cells and adult stem cells. This line of research was pretty controversial for a while (at least in the US) because it results in the creation of embryos just for research purposes, as well as the killing of live embryos. Around 2006, a new type of stem cell, called induced pluripotent stem cells, was discovered and is popularly used today. 

Embryonic Stem Cells

About 2-8 weeks after a human egg is fertilized, the unborn offspring is called an "embryo." Early on in this period, cells start dividing, but remain unspecialized (i.e., blastomeres). These blastomeres can still grow up to be anything they want to be, like a neuron, bone cell, gut cell, etc. Once the embryo becomes implanted on the uterine wall though, these cells quickly start specializing. 

So what do researchers do? They take an unspecialized bundle of cells, referred to as the "inner cell mass," out of its normal environment and move them to an experimental environment. Here, they can replicate themselves continuously and become any cell in the body with the right experimental conditions.

Adult Stem Cells

In adults, stem cells are rare, so not commonly used in research. These cells can also replicate for a long period of time, but result in specialized cells. If you take a look at the "Taste" page, you can read an example of adult stem cells in the tongue. Before adult stem cells become specialized, they go through an intermediate cell stage where they are a "precursor" or "progenitor."  ​There is some evidence that adult stem cells can be manipulated at the precursor stage to specialize in functions that they were not originally intended for (called plasticity).

Induced Pluripotent Stem Cells

It's kind of unbelievable, but researchers actually found a way to take specialized adult cells and and genetically reprogram them into stem cells. How does this happen? Well, researchers take a mature adult cell and add in special genetic information. This genetic information tells the cell to change transcription factor proteins that influence cell function. This form of stem cell therapy raises much fewer ethical concerns than using embryonic stem cells, and solves the problem of poor availability . 

Stem Cell Applications

Lots of research is going on in how to apply stem cells for clinical treatment. With induced pluripotent stem cells, the dream is to take easily accessible adult cells, like skin cells, and use them to create individualized treatments for patients whose symptoms come from the dysfunction of cells (e.g., Parkinson's disease, cardiovascular disease, cancer, etc.).

When does neurogenesis happen?

It’s probably no surprise that lots of new neurons form during the development of a human embryo. What might be more surprising is evidence that suggests neurogenesis can still happen in human adults, thanks to cell functions like long-term potentiation.

What happens after a neuron is born?

After their birth, neurons travel to regions of the brain where they will live out the remainder of their life as specialized workers in a process called differentiation. For example, some neurons might specialize in processing sensory information, while other become involved in motor functions. Research suggests that only about 1/3 of new neurons actually survive to migrate to this final destination. For the neurons that do survive, their exact lifespan is still unknown. It is possible, though, that healthy neurons can surpass their organism’s lifespan (at least from evidence in animal studies). 

Neuron Death

Some neurons can die prematurely and/or unnaturally. This type of neuron death is seen in people who have neurodegenerative (“neuro-” = neuron, “-degenerative” = decline) diseases, like Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. It can also be seen in people who have had brain injury through head trauma or stroke. 

 

Depending on where the neuron death happens, an individual might experience different symptoms. For example, someone with Parkinson’s 

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disease might first experience symptoms like tremors as neurons important for movement die, whereas someone with Alzheimer’s disease might first experience problems remembering new information as neurons important for learning and memory die. After certain types of neuron death, cells called “macrophages” act as janitors by removing the remains of the dead neuron.     

References

[1] US-NIH "Stem Cell Information"

[2] US-NIH "Stem Cell Information: Embryonic Stem Cells"

[3] US-NIH "Stem Cell Information: Adult Stem Cells"

[4] Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 126(4), 663-676.

[5] Lo, B., & Parham, L. (2009). Ethical issues in stem cell research. Endocrine reviews, 30(3), 204-213.

[6] Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. nature, 414(6859), 105.

[7] Hutchins, J. B., & Barger, S. W. (1998). Why neurons die: cell death in the nervous system. The Anatomical Record: An Official Publication of the American Association of Anatomists, 253(3), 79-90.

[8] Gross, C. G. (2000). Neurogenesis in the adult brain: death of a dogma. Nature Reviews Neuroscience, 1(1), 67.

[9] Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998). Neurogenesis in the adult human hippocampus. Nature medicine, 4(11), 1313.

[10] Queensland Brain Institute:“What is neurogenesis?”

[11] US NIH NINDS “The Life and Death of a Neuron”

[12] Magrassi, L., Leto, K., & Rossi, F. (2013). Lifespan of neurons is uncoupled from organismal lifespan. Proceedings of the National Academy of Sciences, 201217505.

[13] Fricker, M., Tolkovsky, A. M., Borutaite, V., Coleman, M., & Brown, G. C. (2018). Neuronal cell death. Physiological reviews, 98(2), 813-880.