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.

Snapshot: How Do Scientific Articles Get Published?

The process of publishing a scientific article begins when a group of scientists set out to answer an outstanding question in their field. They then design and conduct a set of experiments to answer this question. Once the scientists feel that their results answer their questions, one of them – usually the one who did the largest number of experiments in the project – writes a first draft of their article.

Writing the Draft

This article draft is then read and edited by the other researchers who contributed to the experiments described in the paper. They will also be listed as its authors. Once all the article’s co-authors have agreed on a version of the article that they are satisfied with, they may choose to post it on a preprint server. This is an online forum where researchers can post scientific articles that have not yet been accepted for publication in a scientific journal. You can learn more about the differences between preprints and peer-reviewed articles in our past Snapshot on Preprints.

Getting Feedback: The Peer-Review Process

Whether or not the authors decide to post their article to a preprint server, they eventually send it to a scientific journal for publication. Different journals publish different types of articles, and the first thing that the journal’s editor will do is to check that it fits with what that journal usually publishes. This includes considerations like the field of science that the paper falls into, or the techniques used. If the editor accepts the paper, they then send it to a panel of scientists – usually two or three – who are experts in the article’s topic of research. These scientists – known as reviewers – read the paper and assess its quality. This includes asking questions like:

Did the authors do the right experiments to answer the questions that they were asking?

Were the experiments done correctly, or were mistakes made?

Do the results of the authors’ experiments mean what the authors claim that they mean?

The reviewers then send the editors a list of comments about the paper. These comments may include questions about the experiments, disagreements about what the experiments’ results mean, and requests for the authors to do new experiments to strengthen their conclusions.

If the reviewers think that it would take too much work to make the paper ready for publication in the journal, they will recommend that the editor reject the article. If this happens, the authors choose another journal to send their article to. That journal’s editor distributes the article to a new set of reviewers, and the review process begins again.

A notebook and pen lay next to a laptop with a fresh mug of coffee next to them.
What does it take to get a scientific paper published? There is a lot of writing and rewriting involved. Photo by Pixabay on Pexels.com

Revisions and Acceptance

If, on the other hand, the reviewers do not reject the article, the authors are given a set amount of time – usually several months – in which to respond to the reviewers’ comments. This could include doing new experiments, rewriting sections of the paper, and/or writing a response to the reviewers’ comments. The article may be sent between authors and the journal’s reviewers several times. However, once the reviewers all agree that their concerns about the paper have been addressed, the paper is deemed ready for publication. After additional formatting by copy editors, the paper is published in the next virtual and/or physical issue of the journal.

Between writing and rewriting a paper, having it read by multiple people, and doing new experiments, the process of publishing a scientific article can take months or even years! This is especially true if it ends up being sent to multiple journals. In the end, though, this process holds scientists accountable to their peers, allowing us all to be more confident in the findings of scientific research.

If you would like to learn more about scientific publisishing, take a look at this resource by the Understand Science.

Snapshot written by Amy Smith-Dijak  and edited by Celeste Suart.

Snapshot: What is Protein Degradation?

The Life Cycle of a Protein

No protein is made to last forever. Just as DNA and RNA direct a coordinated process for protein creation, there is also a process for proteins to be broken down by the cell. We call this proteolysis or protein degradation.

Proteins are broken down for a number of reasons. First and foremost, it’s a strategy for quality control. After a string of protein building blocks are put together, they are bent and folded into a  specific shape that allows the protein to interact with other proteins in a useful way. You can think of it like a daisy in a daisy chain- the stem needs to be carefully folded and tied or the daisy chain falls apart entirely. Cells have tools to identify misfolded proteins and break them down quickly to prevent problems.

Even beyond quality control, proteins have a certain lifespan within the cell. Regular protein recycling ensures that there is always an available supply of protein building blocks for the creation of new proteins. Removing older proteins also gives cells flexibility in terms of adjusting to environmental changes.

A bright blue plastic recycling bin.
Reuse and recycle. Protein degradation is how your cells break down old or broken proteins so their parts can be reused.
Continue reading “Snapshot: What is Protein Degradation?”

Mutated ataxin-1 protein forms harmful, doughnut-shaped aggregates that are not easily destroyed

Written by Brenda Toscano Marquez   Edited by Marija Cvetanovic

Insoluble clumps of mutated ataxin-1 capture essential proteins and trigger the creation of toxic reactive oxygen species.

All proteins produced by our cells consist of long chains of amino acids that are coiled and bent into a particular 3D structure. Changes in that structure can cause serious issues in a cell’s function, sometimes resulting in disease. Spinocerebellar ataxia type 1 (SCA1) is thought to be the result of one such structural change. The cause of SCA1 is a mutation that makes a repeating section of the ATXIN1 gene abnormally long. This repeated genetic code, “CAG,” is what encodes the amino acid glutamine in the resulting ataxin-1 protein. Therefore, in the cells of patients with SCA1, the Ataxin-1 protein is produced with an expanded string of glutamines, one after the other. This polyglutamine expansion makes the mutated ataxin-1 protein form clumps in many different types of cells – most notably, though, in the cells most affected in SCA1: the brain’s Purkinje cells.

Recent research suggests that these clumps, or “aggregates,” not only take up space in the cell, but that the act of ataxin-1 proteins clustering together might even be beneficial in early stages of disease (it’s possible that the proteins wreak less havoc when they’re in large clumps, rather than all floating around individually). However, another line of research suggests that ataxin-1 aggregates might also be toxic, triggering signals that lead to the cell’s death. As such, how exactly these aggregates affect the deterioration of cells has remained an important question in SCA1 research.

n a search for answers, an international team led by Stamatia Laidou designed a unique cell model of SCA1 to track the development of ataxin-1 aggregates. Their study, published in a recent paper, made use of normal human mesenchymal stem cells that had been engineered to make a modified version of the ataxin-1 protein. In these cells, ataxin-1 was produced not only with the SCA1-causing expansion, but also with a marker protein attached to its end. This marker, known as “green fluorescent protein” (GFP), is used extensively in biological research because it glows under fluorescent light.

doughnut with white and pink sprinkles
Laidou and colleagues have observed mutated ataxin-1 clumps that cause cell stress. Photo by Tim Gouw on Pexels.com

Using this to their advantage, Laidou and her team used a fluorescent microscope to follow the formation of ataxin-1 aggregates over the course of 10 days. The abnormal protein first started accumulating in the nucleus as small dots. As time went on, these dots started blending together, increasing in size. By ten days, the ataxin-1 aggregates had grown even more, forming a doughnut-shaped structure that occupied most of the cell’s nucleus – a crucial structure that houses the cell’s genetic information. These results were intriguing, since the accumulation of normal, non-expanded Ataxin-1 protein does not result in an aggregate with a doughnut shape.

Continue reading “Mutated ataxin-1 protein forms harmful, doughnut-shaped aggregates that are not easily destroyed”

International Ataxia Awareness Day 2020

logo of International Ataxia Awareness Day: a globe with multiple people from around the world marked on it
Image courtesy of the National Ataxia Foundation.

Today marks International Ataxia Awareness Day, which is celebrated every year on September 25th. IAAD brings people together from around the world to raise awareness about this group of rare diseases and to raise money for continuing research efforts.

Here at SCAsource, we are celebrating International Ataxia Awareness Day 2020 by highlighting our top ten most-read articles from this year. We hope you enjoy reading these throwbacks!

10. A New Use for Old Drugs

Basic biology helps identify a new treatment for ataxia. Work from groups in Michigan and California show in mice that not all medications that improve disease symptoms in the short term will continue to do so in the long term

9. How an ataxia gene increases the risk for Alzheimer’s disease

In a tour de force study, a collaborative team of scientists led by Dr. Rudolph Tanzi (Harvard Medical School) and Dr. Huda Zhogbi (Baylor College of Medicine) found a novel relationship between the Spinocerebellar ataxia type 1 gene (ATXN1) and Alzheimer’s disease.

8. A Potential Treatment for Universal Lowering of all Polyglutamine Disease Proteins

One drug to treat them all: an approach using RNA interference to selectively lower the amount of mutant protein in all polyglutamine diseases. Work by a group in Poland shows initial success in Huntington’s Disease, DRPLA, SCA3/MJD, and SCA7 patient cells.

7. A novel gene therapy-based approach with therapeutic potential in SCA3

Cholesterol to the rescue: An alternative approach to treating SCA type 3 using gene therapy.

6. Snapshot: What is Omaveloxolone?

A new therapeutic compound shows promise to treat Friedrich’s Ataxia. But what exactly does Omaveloxolone do in the body? What next steps are being taken to test it?

5. Byproducts of canola oil production show therapeutic potential for MJD and Parkinson’s Disease

Collaboration between researchers in Portugal and the United Kingdom discovers that a canola oil by-product shows promise, corrects MJD/SCA3 and Parkinson’s Disease symptoms in animal models.

4. Snapshot: The next-generation of CRISPR is prime editing – what you need to know

The CRISPR gene-editing toolbox expanded with the addition of prime editing. Prime editing has astounding potential for both basic biology research and for treating genetic diseases by theoretically correcting ~89% of known disease-causing mutations.

3. Two or more birds with one stone: Designing a single therapeutic strategy to treat multiple types of spinocerebellar ataxia

A newly-proposed treatment strategy might be effective against several forms of spinocerebellar ataxia and other CAG repeat-associated disorders

2. Sunrise of Gene Therapy for Friedreich’s Ataxia          

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.

1. Gene Therapy Validated In Human SCA3 Stem Cells

A research group in Michigan report the creation of the first NIH-approved human cell model that mirrors SCA3 disease features – cellular defects that, after gene therapy, show improvement