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Fluorescent mouse blood will help us learn about brain diseases

This is indeed the case. Both animals have proteins in their bodies that allow them to light up.

Researchers at the University of Copenhagen have now invented a way to use these fluorescent proteins to gain new insights into brain diseases such as depression, Alzheimer’s disease and stroke.

“We have been developing for months a new method to visualize blood flow in the brains of experimental mice,” says Hajime Hirase, a professor at the Center for Translational Neuromedicine at the University of Copenhagen. He is one of the researchers behind the new method.

Before the newly developed method, researchers used chemical dyes instead. This dye allowed blood flow in the brain to be observed for only a few hours at a time.

Antonis Asiminas, Marie Curie Fellow, who also worked on the method, adds that the method offers completely new possibilities for monitoring disease progression over time.

“There is already evidence that blood flow is affected by several diseases. It is therefore a tool that can be used in many of them, especially in the long-term progression of diseases. »

Less stress for mice

Because the new method causes the mice to produce harmless fluorescent proteins to tag their blood, rather than chemical dyes, the mice only need to be given an injection once rather than multiple times and every few hours. . This reduces the mice’s stress and pain.

“The rat tail has very thick blood vessels into which we normally inject dyes. So if we look under a microscope, we can see blood that’s well marked, but it only lasts for an hour or two. Our new method labels blood for months. “says Hajime Hirase.

By using fluorescent proteins instead, researchers can better implement the “3Rs,” which are principles for the ethical use of animals in research. The principles aim to refine animal testing, reduce the number of animals in research and, in some cases, replace animals altogether with other methods.

“It addresses two of the three Rs. It’s both a refinement, because we reduce the animals’ stress, but it’s also a reduction, because we can repeatedly do longer studies on the same animal, which also reduces the number of animals,” explains Antonis Asiminas.

The researchers are using mice because they have similar biology to humans, and there are many valuable mouse models for human disease in which the researchers can use their new method.

Activates blood fluorescence by the liver

Blood contains a large amount of albumin, a protein made in the liver. To make blood fluoresce, the researchers took the gene for a fluorescent protein and attached it to the gene for albumin. This fluorescent albumin gene is then packaged into a genetically engineered virus. When mice are injected with this virus, their blood fluoresces. This genetically modified virus does not cause disease and cannot spread to other animals or humans.

“Half of the blood is made up of blood cells and the rest is a liquid called plasma. My graduate students Xiaowen Wang and Christine Delle calculated that if we label a small percentage of albumin, we should be able to see green blood that fluoresces under a microscope,” says Hajime. Hirase and Antonis Asiminas add:

“We package the modified genes that contain albumin and fluorescent protein information into a virus that we inject into the animal. The virus enters the liver and causes the liver to produce the modified protein which ultimately causes the blood to fluoresce. ”

Using a process that occurs naturally in the body, they can trick the liver of mice into causing the blood to fluoresce. This allows you to study blood flow in the brain.

“It’s a way for us to really study the disease in a way that we couldn’t do before. The aim and purpose is that this gives us a new insight into the progression and development of the disease, for example in strokes, which will hopefully lead to a better understanding and possible treatment,” explains Antonis Asiminas.

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