New Microscopy Method Enables Detailed Whole Brain 3D RNA Analysis

Despite significant advancements in RNA analysis, linking RNA data to its spatial context, particularly in intact, detailed three-dimensional (3D) tissue volumes, has remained a challenging task. Researchers have now developed a microscopy technique that allows for detailed 3D RNA analysis at the cellular level within whole, intact mouse brains. This new method, known as TRISCO, has the potential to revolutionize our understanding of brain function in both healthy and diseased states, as demonstrated in a study published in Science.

The TRISCO technique, developed by researchers at Karolinska Institutet (Stockholm, Sweden) and Karolinska University Hospital (Stockholm, Sweden), enables 3D RNA imaging of entire mouse brains without requiring the brain to be sliced into thin sections, which was a necessary step in previous methods. In the study, up to three different RNA molecules were analyzed simultaneously. The researchers plan to expand this technique to analyze approximately one hundred RNA molecules using multiplex RNA analysis, which could provide even deeper insights into brain function and disease mechanisms.

The TRISCO method opens up new avenues for studying the intricate complexity of the brain, potentially leading to the development of novel treatments for a variety of brain disorders. While the study focused on intact mouse brains, it also shows that the TRISCO method is adaptable to larger brains, such as those of guinea pigs, as well as various tissues, including the kidney, heart, and lungs.

“This method is a powerful tool that can drive brain research forward. With TRISCO, we can study the complex anatomical structure of the brain in a way that was previously not possible,” said Per Uhlén, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and the study's last author.