Researchers have introduced an innovative microscopy technique that allows for intricate three-dimensional (3D) analysis of RNA at a cellular level within entire, unaltered mouse brains. This new approach, known as TRISCO, holds the promise of significantly enhancing our comprehension of brain functions under normal and pathological conditions, as detailed in a recent publication in Science.
A team from Karolinska Institutet and Karolinska University Hospital has unveiled a pioneering microscopy method that facilitates detailed three-dimensional (3D) RNA examination at the cellular level within whole intact mouse brains. This new technique, named TRISCO, could greatly reshape our grasp of brain operations in both healthy and diseased states, according to recent findings published in Science.
While advancements in RNA analysis have progressed significantly, correlating RNA information with its spatial surroundings has long presented difficulties, particularly in preserving three-dimensional tissue structures. The TRISCO method now enables researchers to conduct 3D RNA imaging of complete mouse brains without needing to slice the specimens into thin sections, a step that was previously necessary.
“This technique is an essential instrument that can propel brain research to new heights. With TRISCO, we can investigate the brain’s intricate anatomical architecture in ways that were once unattainable,” states Per Uhlén, a professor in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and the study’s senior author.
The researchers in this study examined up to three distinct RNA molecules at once. Their next objective is to expand the scope to study around one hundred RNA molecules through a method called multiplex RNA analysis. This advance could yield even finer insights into brain functions and various disease conditions.
The TRISCO methodology presents fresh opportunities to delve into the intricate nature of the brain, which could, in turn, assist in developing new interventions for an array of brain disorders.
“We are eager to continue our investigation and uncover the vast potential that this novel technique offers,” remarks Shigeaki Kanatani, a research specialist in Uhlén’s lab and the primary author of the study.
Besides being applicable to intact mouse brains, the study confirms that TRISCO can be utilized to explore larger brains, such as those from guinea pigs, as well as various tissues including the kidney, heart, and lung. This research is a collaborative effort between Karolinska Institutet and Karolinska University Hospital.
“Our laboratory maintains multiple partnerships with clinicians actively working at Karolinska University Hospital. Collaboration and mutual understanding between basic researchers and clinicians is vital for advancing biomedical research,” emphasizes Per Uhlén.
The research was supported by funding from the Swedish Research Council, the Swedish Brain Foundation, and the Swedish Cancer Society. Some co-authors are associated with and possess shares in the Danish company Gubra, though no other conflicts of interest have been declared.
