Analysis of molecules that travel from the brain into the blood could enable noninvasive monitoring of gene expression in the organ, according to research published in Nature Biotechnology.
Monitoring gene expression in the brain could generate insights into cognitive behaviors and the onset of neurological diseases. However, the tools available for monitoring the living brain are limited. Researchers have developed tools based on MRI, ultrasound, and other technologies, but they have limitations such as low sensitivity. The analysis of brain tissue is more sensitive, but it is also invasive.
As such, there remains a need for a method that is noninvasive, sensitive enough to measure expression in a small number of cells anywhere in the brain, repeatable, capable of simultaneously imaging multiple molecule types, and inexpensive and accessible to many research laboratories.
The Nature Biotechnology paper describes an attempt to develop such a test by monitoring engineered reporters called released markers of activity (RMAs). Neurons secrete the genetically-encoded reporters of gene expression into the interstitial space of the brain. From there, RMAs cross the blood–brain barrier and enter the bloodstream.
Once RMAs are in the blood, they can be detected using any sensitive biochemical method. Scientists at Rice University showed the potential of the method by expressing RMAs in multiple regions in the brains of mice and then measuring their levels in blood samples. The approach was sensitive enough to detect RMAs expressed by tens to hundreds of neurons.
Jerzy Szablowski, an assistant professor of bioengineering at Rice, outlined how the sensitivity of the blood test and its ability to track changes in specific cells could improve understanding of the brain in a statement.
“Being able to track different gene expression changes will allow us to understand what leads to disease and how the disease itself changes gene expression in the brain. This could provide new clues for drug development, or even for how to prevent neurological diseases in the first place,” Szablowski said.
Szablowski also sees applications in the monitoring of therapies that target the brain. The RMA platform could monitor the effect of gene therapies in the brain to assess the durability of the potential one-time treatments.