Glial Cells, Neurons, Astrocytes and Amyotrophic Lateral Sclerosis

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. Without neuron activity our bodies or body parts couldn’t function. Neurons need the help of glial cells in order to do their job.

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 vital functions.

Glial cells are also called neuroglia or simply glia. The glial cells support and protect the neurons, supply them with nutrients and maintain a suitable chemical environment for them. They also communicate with the neurons and influence their behavior. Some scientists feel that glial cells should actually be thought of as neuron partners rather than neuron supporters. Glial biology is a rapidly expanding field of study.

There are several types of glial cells. Researchers are discovering that damage to one type, known as an astrocyte, contributes to or causes at least some cases of amyotrophic lateral sclerosis, or ALS. ALS is a neurodegenerative disease and is also known as Motor Neuron Disease, Motor Neurone Disease, and Lou Gehrig’s Disease, after the New York Yankees baseball player who suffered from the illness.

The three mains 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, 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. The neurotransmitter travels across the tiny space that exists between neurons to trigger - or sometimes inhibit - a nerve impulse in the next neuron. The region where one neuron ends and another begins is called a synapse. Glial cells affect the activity in a synapse.

The body’s central nervous system (CNS) is made of the brain and spinal cord. The peripheral nervous system (PNS) consists of nerves that travel into and out of the central nervous system, connecting it to other areas of the body. Four types of glial cells in the CNS are astrocytes, microglia, oligodendrocytes and ependymal cells. Glial cells are present in the PNS as well as the CNS. The most common type of glial cell in the CNS is the astrocyte. The brain actually contains more glial cells than neurons.

An astrocyte is shaped like a star and has tentacle-like projections that connect to neurons. Astrocytes are found between the neurons and have many functions. For example, they supply neurons with a range of nutrients and control the concentrations of ions around the neurons. Like neurons, astrocytes make neurotransmitters. At a synapse the astrocytes release, absorb and transport neurotransmitters, including glutamate, affecting the transmission of the electrical signal. Glutamate is an important excitatory neurotransmitter in the nervous system but is toxic to nerves at high concentrations. Astrocytes also play a role in controlling blood flow to the brain. They communicate with each other by means of chemicals.

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.

Motor neurons control muscle movements, breathing, speaking, chewing and swallowing. The upper motor neurons, located in the brain, send nerve impulses to the lower motor neurons in the brain stem and spinal cord. The dendrites and cell body of a lower motor neuron are located in the central nervous system, while the axon extends out of the CNS and towards the muscles.

In amyotrophic lateral sclerosis upper and lower motor neurons degenerate and die. The afflicted person has trouble speaking, swallowing, moving and breathing. 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. Most patients develop ALS in their forties and older, although younger people can also be affected.

There are two categories of amyotrophic laterial sclerosis - familial ALS, which is inherited and accounts for about ten percent of ALS cases, and sporadic ALS, which is not inherited and accounts for about 90% of ALS cases.

Medications used to treat ALS patients may extend the patient's life for a few months, although there are clinical tests being performed on drugs that seem to be more effective. Using the present medications, most patients die within five years of diagnosis, although some people live for up to ten years. One famous ALS survivor is the physicist Stephen Hawking, who was born in 1942 and developed ALS when he was only 21 years old. As of 2011 he has suffered from the disease for 48 years and is still alive, although his symptoms have slowly worsened over time.

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, while 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 is made by the mutated astrocytes.

It's not known if astrocyte problems destroy motor neurons in all patients with ALS, but scientists hope that their studies of mutant astrocytes will help them understand the relationships between astrocytes, motor neurons and ALS better, and that their discoveries will lead to the creation of improved treatments for all cases of amyotrophic lateral sclerosis.

New drugs for treating amyotrophic lateral sclerosis are undergoing clinical tests. These drugs include substances that reduce glutamate toxicity and inflammation. Both these factors are thought to be involved in neuron damage in ALS.

In lab experiments scientists have triggered stem cells to become motor neurons. A stem cell has the ability to develop into other cell types. The goal 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, and it would be easier to add new astrocytes to a patient's body than new motor neurons.

In the not too distant future, motor neurons made from stem cells, healthy astrocytes made from stem cells or effective drug therapy to prevent the toxic action of damaged astrocytes on motor neurons or to prevent glutamate toxicity might be breakthrough treatments for ALS.

Unlike other glial cells, which are made in the nervous system, microglia are made in the bone marrow and then migrate to the CNS. They destroy dead neurons and pathogens (disease-causers like bacteria and viruses) within the nervous system. Microglia are mobile cells and scan the brain for problems, becoming active when a pathogen or brain damage is detected and removing the invader or debris. However, as is the case for other glial cells, scientists currently think that microglia may do more jobs than we give them credit for. It's been noticed that microglia stop moving when they arrive at synapses. Scientists think that they are monitoring synaptic conditions.

Oligodendrocytes produce myelin, a fatty material that surrounds and electrically insulates the axons of neurons, allowing the nerve impulse to be transmitted effectively and rapidly. The cell membrane of the oligodendrocyte, which contains the myelin, wraps itself around the axon multiple times, forming layers of membrane and myelin. Schwann cells have the same function as oligodendrocytes, but are found in the peripheral nervous system.

Ependymal cells line the cavities in the brain and the canal in the center of the spinal cord. They are thought to help make and move the cerebrospinal fluid. This fluid protects the CNS from injury when the body is hit, supplies nutrients to the CNS and removes wastes.

The human nervous system is extremely complex, and understanding how it operates is very difficult. The pace of glial cell and ALS research is increasing, however, so hopefully people with neurodegenerative problems will soon be able to benefit from the new discoveries.

Motor Neuron Diseases Fact Sheet

Toxic Neighbors: Astrocytes Trigger Neuron Death in ALS

Mechanisms of Disease: Astrocytes in Neurodegenerative Disease