Snapshot: What are Astrocytes?

The human brain contains about 170 billion cells. Half of these are neurons and the other half are lesser known cells called glia. Glial cells include astrocytes, oligodendrocytes and microglia. Astrocytes tile the entire brain and interact closely with neurons. Astrocytes are very important for neuronal function, in many ways playing a parenting-like role. They provide energy and support to neurons, and they clean after them. Astrocytes make sure that neuronal surroundings are “just right” for optimal function of neurons. They can also actively influence neuronal activity.

An astrocyte cell grown in tissue culture stained with antibodies to GFAP and vimentin. The GFAP is coupled to a red fluorescent dye and the vimentin is coupled to a green fluorescent dye. Both proteins are present in large amounts in the intermediate filaments of this cell, so the cell appears yellow, the result of combining strong red and green signals. The blue signal is DNA revealed with DAPI, and shows the nucleus of the astrocyte and of other cells in this image.
An astrocyte cell imaged using a microscope and colored antibodies. Imaged courtesy of Wikimedia.

Similar to neurons, there are important differences in astrocytes from different brain regions. For instance, in the cerebellum there are about 5 times more neurons than astrocytes. Meanwhile in the cortex there are 10 times more astrocytes than neurons. In addition, astrocytes in the cerebellum and hippocampus (a brain region that plays an important role in memory) express different sets of proteins. These brain region differences can contribute to the role that astrocytes play in neuronal function in health as well as in disease.

Bergman Glia: An Important type of Astrocyte in Ataxia

In the cerebellum, there is a special type of astrocyte called Bergman glia that are very closely connected with Purkinje cells, neurons that are often vulnerable in ataxia. In fact, the relationship between Purkinje cells and Bergmann glia is often referred to as the most intimate neuron-astrocyte relationship in the brain. This is important as in brain injury and neurodegenerative diseases astrocytes undergo process called gliosis that changes their function. Gliosis can make them either more neuroprotective (helpful) or harmful.

For instance, when there is disease Bergmann glia can increase their support to help Purkinje neurons maintain their function and delay onset of disease symptoms. But also, Bergmann glia can become harmful worsening the dysfunction of Purkinje neurons and more severe disease symptoms.

Bergmann glia  help support Purkinje cells early on in ataxia, but as the disease progresses they can actual make symptoms worse.
Illustrating intimate relationship between Bergmann glia (BG) and Purkinje cells (PC). Bergmann glia may increase their support to Purkinje cells early in disease. However, they can become harmful with disease progression. Image desgined by Marija Cvetanovic.

It is important to learn more about how astrocytes are altered in ataxia for these reasons. We can use that knowledge about astrocytes to develop novel therapies to delay onset of ataxia symptoms and their severity.

If you would like to learn more about astrocytes, take a look at these resources by Khan Academy and Tempo Bioscience.

Snapshot written by Dr. Marija Cvetanovic and edited by David Bushart.

Snapshot: What is a Gene?

A gene is the basic physical unitof heredity. Every living cell contains genetic information that determines an organism’s development, form, and function. This genetic information is encoded by two macromolecules: DNA and RNA.

DNA consists of two strands of phosphate and sugar molecules connected by pairs of nitrogenous bases to form a double helix structure. The four nitrogenous bases in DNA are adenine, thymine, cytosine, and guanine (abbreviated A, T, C, and G). Genes are sequences of nucleotides (composed of a sugar, a phosphate group, and a base) that provide the instructions that cells need to make molecules that give rise to an organism’s characteristics. Within the nucleus of each cell, DNA is tightly coiled around specialized proteins called histones, forming compact structures called chromosomes. Each gene occupies a particular position, or locus, on a chromosome.

In your cells, you find your DNA in tightly packed X shapped molecules called chromosomes. If you unwind this DNA, you can see it is made of of nucleotide bases.
Genes are sequences of nucleotides that give rise to an organism’s traits. DNA is tightly coiled around structural proteins and compressed to form chromosomes. Chromosomes are housed in the cell’s nucleus and replicated prior to cell division. Figure created by Chloe Soutar using Biorender.com.

Most genes contain instructions for creating proteins, amino acid-based macromolecules with a wide range of structures and functions. Among their numerous essential functions, proteins contribute to cell structure and repair, signal transmission between cells, and biochemical reactions within cells. Genes are used to create proteins through a two-step process. Double-stranded DNA is first transcribed into single-stranded messenger RNA (mRNA) that serves as a template for protein synthesis. mRNA exits the nucleus and interacts with cellular machinery called ribosomes. Ribosomes then read mRNA and translate its nucleotide sequence into long chains of amino acids, which then fold to form proteins.

DNA is the instructions to make mRNA, which makes amino acid chains that come together to make protiens which build our bodies.
Genes encode proteins through a two-step process. During transcription, enzymes within the nucleus build single-stranded mRNA molecules that are complementary to one strand of DNA. At this stage, the base thymine (T) is substituted for uracil (U). During translation, cellular structures called ribosomes “read” the mRNA within the cytoplasm and translate the nucleotide sequence into a sequence of amino acids. Linear chains of amino acids then undergo patterns of folding to yield intricate protein structures. Figure created by Chloe Soutar using Biorender.com.

An organism’s complete set of genetic material is called a genotype. The human genome is estimated to contain between 20,000 and 25,000 protein-coding genes, varying in size from thousands of nucleotides to over 2 million nucleotides. The complete set of observable traits that results from gene expression is called a phenotype. An organism’s phenotype includes all of its outward characteristics, including height and eye colour, as well as less apparent characteristics such as blood group and intelligence. For example, the genes that determine the amount of pigment in my skin are part of my genotype, but my skin colour is part of my phenotype. Whereas one’s genotype is determined solely by biological factors, one’s phenotype is determined by complex interactions between biological and environmental factors. This distinction between genotype and phenotype is evident in the case of identical twins – even though they have the same genotype, they often look and behave differently due to environmental and lifestyle factors.

Continue reading “Snapshot: What is a Gene?”

Snapshot: What is Autophagy?

Autophagy is an important disposal mechanism in our bodies, and it is not as scary as the word sounds. The word autophagy is derived from Greek, with ‘auto’ referring to ‘self’ and ‘phagy’ meaning ‘eating’. Autophagy is important for the growth and development of our cells. It helps to restructure our cells and plays a role in our body’s response to stress, like infection or starvation.

 How does autophagy work?

Autophagy is best compared to a very small recycling depot. Our cells are made of many large and small molecules, also called cellular components. For the sake of our analogy, think of these components as the paper and glue that make up the shipping package from an Amazon delivery. When your Amazon box either is damaged or you no longer have a use for it, you put it in your recycling bin. You will monitor how full or empty it is. When full, it is placed at the curb to be picked up on recycling day.

A high-resolution electron-microscopy image of what an autophagosome looks like in cells. Image from Liza Gross retrieved from Wikimedia.

Your neighbourhood’s recycling pick-up day signals to the city workers what part of the city they need to travel to. The bins outside further specify which houses need their recycling picked up. The contents are taken to the depot, where they are sorted, and the materials can be recycled. Special machinery is used to shred and pulp the cardboard, breaking it down into fibers which are used to make new boxes and other paper products.

When cell components are no longer working properly, like the Amazon box, they must be removed and replaced. Molecules, called protein kinases, monitor how well the cell is working – this is you! Deficits activate these proteins, signaling the need for replacement components and thereby placing your recycling out for pick up. In response to this signal, small pieces of membrane are recruited to an assembly site where they combine to form a half circle – the city workers are here to pick up your recycling! This half circle engulfs the defective cell component(s) and then assembles the rest of the circle to form an autophagosome – your box has finally made it to the depot.

The autophagosome then fuses with the membrane of another storage compartment, called a lysosome, which contains digestive enzymes. These enzymes, like the machinery used to shred cardboard, eat away at the inner membrane of the autophagosome. Once they have worked their way through, they can then target its contents – the cardboard is now being worked into a pulp. The enzymes reduce the damaged goods, inclusive of proteins, into amino acids, sugars, and nucleotides. These products can be either removed from the cell or used for nutrients and energy, just like the processed cardboard fibers reused for other products.

What happens when autophagy does not work?

Looking at spinocerebellar ataxias specifically, some are caused by genes that have a polyglutamine expansion. This type of mutation gives cells the wrong instructions for protein folding. These misfolded proteins huddle together in the brain stem which regulates basic functions like breathing; the cerebellum which coordinates voluntary movements; and the basil ganglia which fine tunes these voluntary movements. When autophagy is working properly, the protein clumps can be cleared away easily. When autophagy is defective, as in spinocerebellar ataxias, the cell cannot get rid of these clusters. The proteins continue to accumulate and are toxic to neurons, contributing to the pathology of neurodegenerative disease.

If you would like to learn more about autophagy, take a look at these resources by the Merriam-Webster and our past Snapshot on Protein Degradation.

Snapshot written by Katie Neuman and edited by Celeste Suart.

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.