A team of researchers at the University of Illinois have designed a new approach to 3D imaging that can capture DNA methylation
The scientists said their proof of concept study conducted on pigs will easily translate to humans as the method uses standard MRI technology and existing biological markers.
The new approach called epigenetic MRI or eMRI aims to open up new avenues of research into how changes mould the brain to allow it to grow, learn and respond to stressful environments. It may also be useful in the study of neurodegenerative processes such as Alzheimer’s Disease.
Scientists have been unable to capture the molecular changes that take place in the living brain over time. Earlier studies have focused on honey bees and other organisms which required the removal of brain tissue or that the animal was dissected for analysis. The Illinois team aimed to use the power of MRI to directly capture the epigenetic changes in live subjects.
The new method centred on the key insight that an essential amino acid called methionine could carry an atomic marker called carbon-13 into the brain. Once in the brain, it can donate the carbon-13 labelled methyl group needed for DNA methylation. It would mark the DNA with a rare isotope of carbon.
Methionine is usually obtained through the diet, so the researchers decided to test the idea that feeding the carbon-13-labelled methionine to the animals in the trial would allow it to pass into the brain and label those regions undergoing methylation.
The carbon-13 signal from living animals is weak, so the team relied on their expertise in MRI and MR spectroscopy to significantly enhance the eMRI signal. The piglets used in the study had more new DNA methylation in the brain a few weeks after birth than they did at birth, and the increase was much greater than expected based on changes in size alone.
MRI scan results
Dr. King Li, professor in the Carle Illinois College of Medicine at the University of Illinois said: “DNA methylation is one mechanism that cells use to regulate which genes are actively expressed. Our DNA is the same from cell to cell and it doesn’t change. But tiny molecules, like methyl groups, are attached to the DNA backbone to regulate which genes are actively being transcribed into RNAs and translated into proteins. DNA methylation is a very important part of the control of gene functions.”
The team tried the method in rodents at first, then moved to work with piglets, whose larger brains are closer to human brains.
“This finding is very encouraging because it reflects what we expect to see if this signal is environmentally responsive,” Li said. “It is known from animal studies that brain regions that are most involved in learning and memory experience more epigenetic changes. There also were regional differences in DNA methylation across the pig brain, just like there are regional differences in classical MRI studies.
“We now expect to apply this technique in humans. Getting this label into the brain is easy and does no harm to the body. We’ll give it to people through the diet and then we can detect the signal.”
