Support cells modify Lou Gehrig's Disease
By Deanna Chieco
Issue date: 4/24/08

Glial cells, the supporting cells of the nervous system, are present everywhere in your brain and spinal cord and help with communication between neurons.

Despite their supportive role in the healthy nervous system, these glial cells can undergo functional changes after a brain injury or during illness that make it harder for the nervous system to heal.

A group of Hopkins researchers led by Nicholas Maragakis, a neurologist at the School of Medicine, examined the role of glial cells in the neurodegenerative disease amyotrophic lateral sclerosis, known as ALS or Lou Gehrig's Disease.

ALS involves the progressive degeneration of motor neurons, which transmit signals from the brain that tell muscles what to do, and eventually leads to weakness, paralysis and death.

The researchers examined how the growth or proliferation of astrocytes, a type of glial cell found throughout the central nervous system, could play a role in the cause of ALS.

Following an injury, astrocytes undergo a process called reactive astrogliosis, in which they lose their normal functioning and exhibit altered gene expression.

In a healthy nervous system, astrocytes play a supporting role which consists of regulating neurotransmitter and ion uptake as well as preventing toxins in the blood from reaching the brain.

However, if astrocytes become reactive, they can lead to the death of their neighboring neurons because of the loss of vital functions.

Working from previous evidence that reactive astrogliosis was important in neurodegenerative disorders, this group of researchers investigated a connection between the proliferation of these reactive astrocytes and ALS.

They used two mouse models that were genetically modified to express either an acute or chronic form of motor neuron disease. Markers were used to label dividing astrocytes in tissue sections for each mouse model. Astrocytes and motor neurons in the lower region of the spinal cord were the main area of focus.

The acute model represents the immediate cellular changes following a traumatic brain or spinal cord injury. In this model, they found that astrocyte proliferation was reduced in the disease model as compared to a wild-type mouse.

However, if these proliferating astrocytes were ablated, or removed, there was not a significant decrease in the number of reactive glial cells.

They concluded that proliferating astrocytes were not a large component of the reactive astrocytes contributing to acute motor neuron disease.

The chronic mouse model, which implies a slower onset and progression of disease-like symptoms, is more representative of ALS. In this case, the number of proliferating astrocytes was also reduced but found not to be the main contributor to reactive astrogliosis.

Additionally, if the proliferating astrocytes were ablated, the disease-like symptoms were retained, indicating that cell death of motor neurons was still occurring.

In each of these models, there was an increase in the number of astrocytes present, though they may not have been actively dividing at the time.

For a chronic disease like ALS, if large numbers of astrocytes proliferate over a long period of time, there could still be a significant effect on astrogliosis.

Though the researchers did not find improved symptoms if proliferating astrocytes were ablated, they were able to better define the role of these astrocytes in terms of nervous system injury and degeneration.

They determined that proliferating astrocytes are a relatively small contributor to the symptoms of the disease, but that they are in fact present in reactive astrogliosis.


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