Glial Cells, Astrocytes, Neurons, and Amyotrophic Lateral Sclerosis (ALS)
What Is Amyotrophic Lateral Sclerosis?
ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that has serious and often heartbreaking effects. As the disease progresses, the patient gradually loses their ability to move, speak, chew, swallow, and breathe. The patient usually dies prematurely due to respiratory failure.
ALS is a frustrating disease because it's poorly understood, and the current treatments aren't very effective. There are signs of hope, however. Researchers have discovered possible explanations for the destruction of motor neurons in ALS patients. These discoveries could lead to better treatments for the disease.
One very interesting area of research with respect to ALS is the role of glial cells, especially astrocytes. Glial cells are abundant in the nervous system but have traditionally been considered to be less important than neurons, the cells that conduct nerve impulses. The glial cells actually play vital roles in keeping neurons alive and in enabling them to function properly.
ALS is of particular interest to me because my mother died from the disease. The latest discoveries are too late to help her, but they may be very helpful for other patients.
More About Glial Cells
The Importance of Glial Cells and Astrocytes
There are two types of cells in the human nervous system: neurons and glial cells. The neurons transmit nerve impulses, which are traveling electrochemical signals. These signals are essential in order to keep us alive. Neurons need the help of glial cells in order to do their job, however.
Glial cells surround neurons. The word “glial" is derived from a Greek word meaning “glue." When glial cells were first discovered, it was thought that their function was simply to hold neurons in place. Until recently, most scientists investigating the nervous system studied neurons instead of glial cells, since neurons were thought to be far more important. Researchers now know that glial cells have many essential functions. The brain actually contains more glial cells than neurons.
Glial cells are also called neuroglia, or simply glia. They support and protect the neurons, supply them with nutrients, and maintain a suitable chemical environment for them. One type—the astrocyte—also influences the behavior of neurons. Researchers are discovering that damage to astrocytes may contribute to at least some cases of amyotrophic lateral sclerosis.
Diagram of a Neuron, or Nerve Cell
Neurons and Synapses
The three main parts of a neuron are the dendrites, the cell body, and the axon. The dendrites receive a nerve impulse from a sensory receptor, or from another neuron, and then send the impulse to the cell body. The cell body, which contains the nucleus and other organelles of the neuron, sends the impulse to the axon. The axon then transmits the impulse to the next neuron or to a muscle or gland. A “nerve” is a bundle of axons.
A chemical called a neurotransmitter is produced by the end of a neuron and stored in sacs called synaptic vesicles. When a nerve impulse reaches the area, neurotransmitter molecules are released from the vesicles. The molecules then travel across the tiny space that exists between neurons and bind to receptors on the next neuron. This union triggers—or sometimes inhibits—a nerve impulse in the second neuron. The region where one neuron ends and another begins is called a synapse.
Neuron and Synapse
Many astrocytes are shaped like a star and have tentacle-like projections that connect to neurons. They are frequently associated with synapses and have many functions, including the ones described below.
- Astrocytes supply neurons with a range of nutrients.
- Astrocytes control the concentrations of ions around the neurons.
- At a synapse, the astrocytes absorb and break down glutamate. Glutamate is an important neurotransmitter in the nervous system. A high concentration of glutamate is toxic to nerves, however.
- Astrocytes make and secrete their own version of neurotransmitters, which are known as gliotransmitters. The exact functions of these gliotransmitters aren't yet known.
- Astrocytes play a role in controlling blood flow to the brain.
More and more astrocyte functions are being discovered, although the exact ways in which they act are not always clear and some of the proposed functions are controversial. For example, one claim is that astrocytes control memory and learning in the brain, which not all scientists support.
The discovery of the importance and multiple functions of astrocytes has led some scientists to refer to a "tripartite" synapse. This involves the presynaptic neuron, which releases a neurotransmitter, the astrocyte, and the postsynaptic neuron, which receives the neurotransmitter. All parts of the synapse are considered to be equally important.
The Functions of Astrocytes
The Central and Peripheral Nervous Systems
The body’s central nervous system (CNS) consists of the brain and spinal cord. The peripheral nervous system (PNS) consists of nerves that travel in and out of the central nervous system, connecting it to other areas of the body. Astrocytes in the CNS outnumber the neurons and are the most abundant cells in the central nervous system.
ALS and Motor Neuron Degeneration
Amyotrophic lateral sclerosis is also known as Lou Gehrig’s disease after the New York Yankees' baseball player who suffered from the illness. Other names for the illness are motor neuron disease and motor neurone disease.
There are two categories of amyotrophic lateral sclerosis:
- Familial ALS, which is inherited (accounts for about 10% of ALS cases)
- Sporadic ALS, which is not inherited (accounts for about 90% of ALS cases)
Both cases involve damage to motor neurons. Motor neurons control the muscles that enable us to move, as well as the ones involved in breathing, speaking, chewing, and swallowing.
Both upper and lower motor neurons may be involved in ALS. The upper motor neurons originate in the brain and are unable to leave the central nervous system. The dendrites and cell body of an upper motor neuron are located in the cerebral cortex, but the axon travels down through the brain into the brainstem or spinal cord. The axon of the upper motor neuron then stimulates a lower motor neuron. The dendrites and cell body of the lower motor neuron are located in the central nervous system. The axon extends out of the CNS and travels to the muscles in a peripheral nerve.
In ALS, upper and/or lower motor neurons degenerate and die. Strangely, some motor neurons don’t degenerate, including the ones that control the urinary bladder and large intestine. The person’s mental faculties are also unaffected in many cases, although some people with ALS develop dementia. Most patients develop ALS in their forties and older, although younger people can also be affected.
ALS and Astrocyte Problems
Astrocytes and Excess Glutamate
An abnormally high concentration of glutamate around neurons has been strongly implicated in the development of amyotrophic lateral sclerosis. The ALS Association says that "abundant evidence" links a high glutamate level to destruction of motor neurons. The only drug recommended for ALS treatment at the moment with respect to extending lifespan is Riluzole. This is believed to work by stimulating glutamate removal from the area around the synapses. The glutamate is normally absorbed by astrocytes. Failure of the astrocytes to do this could be linked to ALS.
Astrocytes and the SOD1 Enzyme
Researchers have discovered that mutated astrocytes present in some patients with familial ALS can cause degeneration and death of motor neurons. The mutated astrocyte gene that has been most studied is the one that normally programs the cell to make an antioxidant enzyme called superoxide dismutase, also known as the SOD1 enzyme.
In lab experiments, motor neurons die when they are cultured with the mutant astrocytes. Other types of neurons in the culture aren’t damaged. In one experiment, mutated astrocytes were grown separately. Some of the growth medium surrounding the astrocytes was then transferred to a container of motor neurons. The neurons died after they were exposed to the medium, suggesting that a toxin was made by the mutated astrocytes. Discoveries in the Iaboratory don't always apply to intact organisms, but they sometimes do.
It's not known if astrocyte problems destroy motor neurons in all patients with ALS. Scientists hope that their studies of mutant astrocytes will help them better understand the relationships between astrocytes, motor neurons, and ALS. They also hope that their discoveries will lead to the creation of improved treatments for all cases of amyotrophic lateral sclerosis.
Living With ALS
Medications used to treat the symptoms of ALS can help a patient feel more comfortable. Riluzole slows the progression of the disease in some patients. There are clinical trials being performed with other drugs that may be helpful. Physical therapy and breathing aids may also be helpful.
Unfortunately, at the moment the average survival time for an ALS patient after diagnosis is two to five years. This means that some people live for a shorter time and some people for a longer time. One of the things that I find sad about this survival prediction is that it hasn't changed since my mother died from ALS, which happened over thirty years ago. There is more research being done today than when my mother was alive, however, which includes investigations into the use of stem cells as a treatment. This research could lead to some very useful developments.
One famous ALS survivor is the physicist Stephen Hawking, who was born in 1942 and developed ALS when he was only 21 years old. He has suffered from the disease for 52 years and is still alive. His symptoms have slowly worsened over time, however. He uses a wheelchair to move around and needs special equipment in order to communicate with others.
Stephen Hawking's long life with ALS is unusual. One of the people from my local ALS society who helped my mother also had a very slowly progressing form of the disease, however. Some researchers think that there are different types of ALS even beyond the familial and sporadic varieties and that the condition may actually be more than one disease.
Stem Cell Treatment for ALS
In lab experiments, scientists have triggered stem cells to become motor neurons. A stem cell is an unspecialized cell that has the ability to develop into other cell types. The goal of the research is to implant motor neurons created from stem cells into ALS patients (or other patients with motor neuron damage) in order to replace their own neurons. This procedure has been carried out successfully in mice, but trials in larger animals and in humans have not yet been done. One problem with this potential treatment is that if we don’t discover what destroyed the neurons in the patient’s body, the new, transplanted neurons could become damaged as well, just like the original neurons.
Some scientists are working on creating astrocytes from human stem cells and feel that this a better plan of action than creating motor neurons from stem cells. They know that astrocytes have a large effect on the health of motor neurons. It would also be easier to add new astrocytes to a patient's body than to add new motor neurons.
In the not-too-distant future, motor neurons or astrocytes made from stem cells or effective drug therapy to control excess glutamate might be breakthrough treatments for ALS.
Stem Cells and ALS
ALS in the Future
Many researchers study the functioning of neurons. This is understandable, because if the neurons become inactive we become incapacitated or die. The functions of the glial cells mustn't be overlooked, however. Research indicates that their activity is vital for maintaining the health and activity of the neurons. Whether malfunctioning of glial cells is the primary cause of ALS or a secondary effect of the main cause, we need to understand the role of the cells in health and in disease.
I've been following the ALS research ever since my mother had the condition. I'm pleased to see more attention being paid to the disease by both researchers and the public. The recent movie about Stephen Hawking's life ("The Theory of Everything") and the Ice Bucket Challenge to raise funds for ALS patients and research are both great forms of publicity.
The human nervous system is extremely complex and understanding how it operates is very difficult. The pace and interest in glial cell and ALS research seems to be increasing, however, so hopefully people with neurodegenerative problems will soon be able to benefit from the new discoveries.
- "Types of glia." University of Queensland Brain Institute. https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/types-glia (accessed August 21, 2017).
- "Disease Mechanisms." ALS Association. http://www.alsa.org/research/focus-areas/disease-mechanisms/ (accessed August 21, 2017).
- Phatnani, Hemali P. et al. "Intricate interplay between astrocytes and motor neurons in ALS." Proceedings of the National Academy of Sciences of the United States of America. http://www.pnas.org/content/110/8/E756.full (accessed August 21, 2017).
© 2011 Linda Crampton