In living color: New technique sees gene activity in human brains

Do not let the pretty tangerine and lemon yellow glow in brain images fool you. If the inventors are right, an elegant new tool neuroimaging offers more than fetching images :. This demonstrates for the first time that genes are activated or deactivated in living brains, scientists reported on Wednesday

Until now, activation of genes in the human brain could be detected only in the dead. By revealing the choreography on and off the DNA in the brains are still thinking, feeling, and remember, the new technique promises to reveal genetic basis of mental health and perhaps one day, to detect the first signs of a brain be grasped by Alzheimer , schizophrenia , or other diseases.

“This is very exciting, pioneering work,” said John Satterlee the National Institute on Drug Abuse, who coordinated the The program of the NIH to study patterns of gene silencing and gene activation, who was not involved in this study. “We were taken to a place he knew nothing about” – patterns of gene expression in human brains live – “and showed us the lay of the land.”


article after the announcement

epigenetic brain – that genes are turned on or off in different structures – has become a hot topic, as neurologists realized that the sequences DNA inherited explain very little about psychiatric illness. In contrast, genes that are activated and off could be important in a wide range of brain disorders, including addiction, Alzheimer’s disease, Rett syndrome , depression and schizophrenia, as well as age-related changes . And because life events can alter genes “on-off state, epigenetic changes could be how the tragedy, trauma, and other experiences cause long-term changes in the brain.

gene activity “is so sensitive to the environment, we simply can not study outside their natural context,” said the chemist Jacob Hooker, of Massachusetts General Hospital, who led the research, published in Science Translational Medicine. “[Dead] brains and the brains of living will be very different. “

the new technique is a cousin of PET. traditional PET detect the emission of subatomic particles called positrons from the radioactively labeled glucose, energy source of the brain, and therefore it reveals what brain regions are active. This version of PET detects positrons from radioactively labeled “Martinostat,” a small molecule Hooker and his colleagues created in 2012 . (Patented and licensed Martinostat.) Administered intravenously, the molecule slips through the blood-brain barrier (thanks to a handful of atoms that “acts like a ball of fat,” Hooker said). Once in the brain, it binds to calls HDACs enzymes that inactivate genes – including genes important in synapse formation and thus learning and memory. PET detects positrons, and ready :. A map showing the brain where the genes are turned off

That could be a first step in the discovery that, in the brain, the lights go out genetic, causing the disease.


Hooker administered Martinostat (named for the Center for Biomedical Imaging at MGH Martino) to eight healthy volunteers. Scientists were trying to show that the technique could work in the brains of living, but beyond that the proof of principle, but also did some preliminary findings.

molecules silenced genes were most abundant in the cerebellum, in the back of the brain that regulates the movements, and putamen, making further coordinate some forms Learning. The gene silencing molecules were less abundant in the hippocampus (memories that form) and amygdala (processing and producing emotions such as anger). It is not clear what could explain the pattern, but one possibility is that the regions with the least amount of these molecules have the greatest potential for “neuroplasticity”, or alteration of its neural connections in response to life the owner of the brain he drives.

More surprising than the differences between brain regions was the unexpected similarity between people. The regions with lots of silencing of genes in a person’s brain regions also had a lot of silence in the brains of others, while regions without much silencing genes were also mostly the same.

Uniformity suggests that there could be a baseline pattern of gene activation in the brain, healthy life. If so, then deviations from this pattern can be used to diagnose diseases before symptoms appear. In the brains of deceased Alzheimer’s patients, for example, the hippocampus is full of gene silencing molecules.

“I’m waiting for these color maps will compare healthy brains with the brains of people with schizophrenia, Alzheimer’s, and other diseases,” the location of regions with aberrant gene expression patterns, Hooker said.

The new PET technique can not identify specific genes are turned off. But that can be done in the dead brains, Hooker said, “and we are trying to indicate what genes are involved” in what conditions.

His team has already used the new imaging technique patterns of gene expression in the brains of nine people with schizophrenia and a few with Huntington’s disease. They have funds to start doing the same with Alzheimer’s patients. The results could show how gene silencing gone wrong explains the conditions and, one day, point the way to treatments. “This is really the first step to be able to look” in the genetic form of on and off signals could cause, or at least be precursors of this type of brain diseases, NIH Satterlee said.

This possibility has already drawn the attention of the biotechnology industry. based in Cambridge, Massachusetts startup Rodin Therapeutics is working on the development of drugs that, by inhibiting enzymes gene silencing could try Alzheimer’s, Parkinson’s, PTSD and . The focus has enough promise that the biotech giant Biogen is willing to pay $ 500 million for that .

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