Snapshot: What is the Rotarod Test?

Patients with ataxia share many common symptoms, including a loss of coordination. While these symptoms might be easy to see in patients, testing movement ability is not as straightforward in mouse models of ataxia. Because of this, researchers use something called the “rotarod performance test” to assess motor coordination and performance in mice.

How do researchers measure ataxia symptoms in mice? Image courtesy of WikiMedia.

What is a Rotarod?

A rotarod is a machine that is similar to a treadmill. It consists of a rod that rotates at a set speed and accelerates for a designated amount of time. During testing, mice are placed on the rod. The spinning of the rod causes the mice to jog. Researchers record the amount of time the mouse spends on the rod.

Mice on a rotating rod, seperated into lanes. Underneath the rod is padding for when the mice fall.
Diagram of Mice on a Rotarod. Image created with BioRender by Eder Xhako.

If a mouse spends less time on the rotarod, it suggests that the mouse has motor coordination deficits that are similar to an ataxia patient’s. Researchers also use the rotarod to assess motor learning in mice: the test is performed over multiple days. This is so they can determine how much motor learning has occurred by comparing how the mice did on the first day versus the last day.

Why do researchers use the Rotarod?

The rotarod allows researchers to measure the coordination and motor learning ability of mice. Having a consistent system of measurement also allows scientists to compare the results of different mouse models. For example, we can see how a new mouse model of ataxia performs compared to mice without ataxia. This allows us to see how severe the motor symptoms are in that specific model. This gives us the ability to confirm that the new mouse strain really does model ataxia.

More excitingly, though, we can use the rotarod to see what effect different treatments have on ataxia symptoms. If a treated mouse is able to spend more time on the rotarod than an untreated mouse, it suggests that the treatment helps improve motor symptoms. Seeing treatment results in a mouse model of ataxia gives researchers more confidence that the same treatment could be useful for patients with ataxia.

If you would like to learn more about the rotarod test, take a look at this video by the Maze Engineers.

Snapshot written by Eder Xhako and edited by Carrie Sheeler.

Spotlight: The Neuro-D lab Leiden

Principal Investigator: Dr. Willeke van Roon-Mom

Location: Leiden University Medical Centre, Leiden, The Netherlands

Year Founded: 1995

What disease areas do you research?

What models and techniques do you use?

A group photo of members of the Neuro-D lab Leiden standing outside on a patio.
This is a group picture taken during our brainstorm day last June. From left to right: Boyd Kenkhuis, Elena Daoutsali, Tom Metz, Ronald Buijsen, Willeke van Roon-Mom (PI), David Parfitt, Hannah Bakels, Barry Pepers, Linda van der Graaf and Elsa Kuijper. Image courtesy of Ronald Buijsen.

Research Focus

What is your research about?

The Neuro-D research group studies how diseases develop and progress at the molecular level in several neurodegenerative diseases. They focus on diseases that have protein aggregation, where the disease proteins clump up into bundles in the brain and don’t work correctly.

We focus strongly on translational research, meaning we try to bridge the gap between research happening in the laboratory to what is happening in medical clinics. To do this we use more “traditional” research models like animal and cell models. But we also use donated patient tissues and induced pluripotent stem cell (iPSC) models, which is closer to what is seen in medical clinics.

Our aim is to unravel what is going wrong in these diseases, then discover and test potential novel drug targets and therapies.

One thing we are doing to work towards this goal is identifying biomarkers to measure how diseases progress over time. To do this, we use sequencing technology and other techniques to look at new and past data from patients.

Why do you do this research?

So far there are no therapies to stop the progression of ataxia. If we can understand what is happening in diseases in individual cells, we can develop therapies that can halt or maybe even reverse disease progression.

Identifying biomarkers is also important, because it will help us figure out the best time to treat patients when we eventually have a therapy to test.

Stylized logo for the Dutch Center for RNA Therapeutics
The Neuro-D lab Leiden is part of the Dutch Center for RNA Therapeutics, which focuses on RNA therapies like antisense oligonucleotides. Logo designed by Justus Kuijer (VormMorgen), as 29 year old patient with Duchenne muscular dystrophy.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for a SCA1 natural history study and biomarker study. More information can be found here. Please note that information about this study is only available in Dutch.

Fun Fact

All our fridges and freezers have funny names like walrus, seal, snow grouse and snowflake.

For More Information, check out the Neuro-D lab Leiden website!


Written by Dr. Ronald Buijsen, Edited by Celeste Suart

Spotlight: The Watt Lab

Watt lab logo of a neuron

Principal Investigator: Dr. Alanna Watt

Location: McGill University, Montreal, Canada

Year Founded: 2011

What disease areas do you research?

What models and techniques do you use?

Research Focus

What is your research about?

We are interested in how the cerebellum influences motor coordination in both the healthy brain and in models of disease and aging. By identifying changes in the cerebellum underlying ataxias and aging, we hope to discover new treatments for patients.

Why do you do this research?

We want to understand how the cerebellum works and use this knowledge to understand the changes in the cerebellum that lead to ataxia. As a lab, we are particularly interested in studying rare disorders like SCA6 and ARSACS.

These disorders have limited treatment options. We hope that by understanding how the cerebellum works differently in these disorders, we will be able to identify new treatments to help ataxia patients.

We are also interested in identifying common changes between different types of ataxia, to find out whether treatments identified in one form of ataxia might also help other ataxia patients.

Six slippers with a variety of designs, includes brain cells and mice

Fun Lab Fact

We got together and made our own slippers to keep cozy in our office. If you look at the picture closely you might be able to spot some cells from the cerebellum on some of them!

Image courtesy of Anna Cook.

For More Information, check out the Watt Lab Website!


Written by The Watt Lab, Edited by Celeste Suart

Sunrise of Gene Therapy for Friedreich’s Ataxia

Written by Dr. Marija Cvetanovic   Edited by Dr. Ronald Buijsen

Researchers from the University of California show they can “edit” the Frataxin gene in human cells from Friedreich’s Ataxia and transplant them into mice. This lays the groundwork for this method to be tested for safety.

Friedreich’s ataxia is a progressive, neurodegenerative movement disorder. It is often associated with heart issues and diabetes. Symptoms first start to appear in patients when they are around 10 to 15 years old. Friedreich’s ataxia has the prevalence of approximately 1 in 40,000 people and is inherited in a recessive manner. This means that patients with Friedreich’s ataxia inherited a disease gene from both the father and mother. Friedreich’s ataxia is caused by an overexpansion of the GAA repeat in the Frataxin gene, all these extra repeats causes less Frataxin protein to be made.

Human hematopoietic stem and progenitor cells (HSPCs) are the stem cells that give make to other types of blood cells. You can find HSPCs in the blood all around the body.

HSPCs are ideal candidates for use in stem cell therapy because of a few reasons. First, you can easily get them out of the body through a blood donation (at least easier than some other types of cells!). Second, they can self-renew, meaning they will make more of themselves. Third, other folks have researched this type of cell before, so we know they are fairly safe. Researchers wanted to test if these cells could be used to help treat Friedreich’s ataxia.

CRISPR-Cas9 is a customizable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. The tool is composed of two basic parts: the Cas9 protein, which acts like the wrench, and the specific RNA guides, CRISPRs, which act as the set of different socket heads. These guides direct the Cas9 protein to the correct gene, or area on the DNA strand, that controls a particular trait. This lets scientists study our genes in a specific, targeted way and in real-time.
Researchers used CRISPR editing to fix the mutation causing Friedreich’s ataxia in patient blood cells. Photo Credit: Ernesto del Aguila III, National Human Genome Research Institute, National Institutes of Health
Continue reading “Sunrise of Gene Therapy for Friedreich’s Ataxia”

Targeting protein degradation to alleviate symptoms in MJD

Written by Ambika Tewari   Edited by Brenda Toscano Márquez

Trehalose, a natural autophagy inducer shows promise as a therapeutic candidate for MJD/SCA3

Every cell has an elaborate set of surveillance mechanisms to ensure optimal functioning. As proteins are synthesized, errors can occur leading to misfolded proteins. These abnormal proteins can be harmful to the cell. For this reasons it is important to monitortheir occurrence and decide whether they should be degraded.  Autophagy is one way that these misfolded proteins can be degraded. Autophagy literally means self-eating and serves as a quality control mechanism. Defects in autophagy have been linked to several neurodegenerative disorders.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 is caused by an abnormal expanded CAG repeat in the ATXN3 gene. This CAG expansion causes misfolding of the ataxin-3 protein. The now unstable ataxin-3 is prone to forming aggregates in cells of some regions of the brain including the cerebellum, brainstem and basal ganglia. The accumulation of ataxin-3 in the cell leads to the progressive loss of neurons in the affected brain regions.

Normal ataxin-1 proteins becomes misfolded due to CAG expansion, but autophagy with proteins LC3B and Beclin-1 should degrade and break down misfolded ataxin-3
A diagram of how autophagy should break down abnormal expanded ataxin-3. But what happens when this break down doesn’t happen? Diagram by  Ambika Tewari using BioRender.

Researchers, eager to help patients with MJD, began to question why would the cellular surveillance system allow this toxic accumulation of misfolded ataxin-3. Surely there are mechanisms, like autophagy, to prevent this from occurring. This led to a number of studies that found that autophagy is defective in MJD patients. This was also confirmed in different mouse and cell models of MJD. In fact, earlier studies by the lab of Dr. Luís Pereira de Almeida found that increasing the amount of an autophagy protein (beclin-1) in the brain of an MJD mouse model improved some of the behavioral and neuropathological deficits. Together, these studies have provided evidence that autophagy may serve as a therapeutic target for MJD.

Continue reading “Targeting protein degradation to alleviate symptoms in MJD”