Genes on the brain H.-Y. Wey et al., Science Translational Medicine (2016)

The switching-off of genes in the human brain has been watched live for the first time. By comparing this activity in different people’s brains, researchers are now on the hunt for abnormalities underlying disorders such as Alzheimer’s disease and schizophrenia.

To see where genes are most and least active in the brain, Jacob Hooker at Harvard Medical School and his team developed a radioactive tracer chemical that binds to a type of enzyme called an HDAC. This enzyme deactivates genes inside our cells, stopping them from making the proteins they code for.

When injected into people, brain scans can detect where this tracer has bound to an enzyme, and thus where the enzyme is switching off genes.


Live epigenetics

The switching-off of genes by HDACs is a form of epigenetics – physical changes to the structure of DNA that modify how active genes are without altering their code. Until now, the only way to examine such activity in the brain has been by looking at post-mortem brain tissue.

In the image above from the study, genes are least active in the red regions, such as the bulb-shaped cerebellum area towards the bottom right. The black and blue areas show the highest levels of gene activity – where barely any HDACs are present – and the yellow and green areas fall in between.

The team found that genes are most active in the hippocampus, which is involved in memory and learning, and the amygdalae, which process fear, pleasure, emotion and motives. These are particularly dynamic areas of the brain that need constant gene activity, so HDAC seems to be almost silent here.

“It’s a good start for determining which epigenetic processes occur in the brain,” says Isabelle Mansuy at the University of Zurich in Switzerland.

Detecting disease

Scanning the healthy brains of eight people, Hooker was surprised how similar the patterns of gene deactivation were between them. “We think of it as a highly dynamic process, so we expected lots of variation between people,” says Hooker. It suggests gene-expression levels are maintained close to a standard pattern, he says.

This could mean that changes in gene inactivation are a sign that something is wrong. Hooker and his team plan to compare patterns from healthy people with those of people who have brain disorders to see if they can detect which genes are involved in these conditions.

“We’ve already scanned seven patients with schizophrenia, a couple with Huntington’s disease, and have funding to scan 40 Alzheimer’s patients,” says Hooker.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aaf7551