Cerebellar Ataxia—The Unbalanced Illness

By: Nicholas Handfield-Jones

It is one of the largest regions of the brain, yet neuroscientists know relatively little about it. About the size of a bar of soap, the cerebellum (Latin for “little brain”) is nestled into the back of the brain and looks like a pile of cooked spaghetti. Anatomists in ancient times like Aristotle and Galen remarked on its distinctive appearance, yet it was not until the 19th century that neuroscientists discovered its role in movement.

People that have suffered damage to their cerebellum can still move, but they become unbalanced and uncoordinated. This is called cerebellar ataxia, and it can be very debilitating to those who suffer from it. It can occur at birth, as a natural part of aging, or from brain trauma. It is estimated that 1 in 10,000 people suffer from cerebellar ataxia. Unfortunately, neuroscientists do not fully understand how it works nor do they agree on a course of treatment. 

The cerebellum (in red). Image by BodyParts3D, © The Database Center for Life Science licensed under CC Attribution-Share Alike 2.1 Japan.

A research team led by Dr. Wei-Yang Lu at Western University has recently discovered new insights into the cerebellum that might help with understanding cerebellar ataxia. In a new article published last year in the journal Cerebellum, the team investigated a new link between nitric oxide and cerebellum function.

Nitric oxide is most commonly thought of as a gas, but in the brain, it can act as an important communication signal between brain cells. These brain cells are called neurons, which act as roads for information, such as instructions to move. To send information from one neuron to the next, neurons send out chemicals called neurotransmitters—which are used to communicate between neurons. If neurons are the electrical wires of a house, neurotransmitters are the light switches, letting the electrical wires know whether to turn on the lights. Nitric oxide is one such light switch.

According to PhD candidate and Western University student Vasiliki Tellios, the lead author of the study, nitric oxide appears in cerebellum neurons more than in any other brain region. Despite this observation, it has not been studied heavily by researchers. “The reason why nitric oxide is so understudied is because it is very hard to work with,” says Tellios. “Because it’s a gas, it’s historically been hard to be totally accurate with it.”

But given the development of advanced microscopic techniques in the last thirty years, nitric oxide can now be examined more easily.

In their study, Tellios and her colleagues examined cerebellar neurons grown in a petri dish that lack nitric oxide. This lack of nitric oxide is known to be associated with cerebellar ataxia, so this petri dish acts as a model for the disease.

What they found surprised them. While the total number of neurons in the dish had not changed due to the lack of nitric oxide, the shape of the neurons themselves had altered dramatically. Healthy neurons will have many branches on them, which allows for more communication. However, they found far fewer branches in these cerebellar ataxia neurons.

Think of it like this. Imagine the cerebellum as a forest, and neurons as the forest trees. In the tissue cultures that mimicked ataxia, the forest had the same number of trees, but the trees had fewer branches. Just as trees with fewer branches are far less healthy than those with many, so too are neurons with fewer branches.

 The exciting new insight into the microscopic role of nitric oxide in the cerebellum provided by Tellios and colleagues could help to develop and improve treatments for cerebellar ataxia. Although nitric oxide itself could be difficult to administer to patients, perhaps the molecule that creates it in the body (called neuronal nitric oxide synthase, or nNOS), could be a potential avenue, as it is much more stable.

 Though the experiment was challenging, Tellios explains that it was fascinating to work with an understudied molecule in an understudied brain area.

“Living with ataxia can be painful,” Tellios tells me. “Figuring out what proteins and what pathways can be targeted to remedy ataxia is important in the long run because right now there is no definite treatment, and any bit of evidence can help.”