Human brain imaging technology uncovers the mysterious brain and helps treat mental illness

Release date: 2016-08-16

Scientists believe that the level of HDAC is related to the degree of genetic change. The brain region with the highest HDAC content is also the brain region where the genes are least likely to change. Therefore, high levels of HDAC can impede human learning, even in normal human brains.

New human brain imaging techniques will reveal how genes activate active human brains.

For the first time, scientists have used brain scanning techniques to reveal changes in the brain's activity, a finding that will help treat Alzheimer's syndrome, schizophrenia, and other diseases caused by brain disorders. This is not all, and further research will help researchers assess the efficacy of drugs on these diseases.

"Genetic or environmental"

Researchers from Harvard Medical School are focusing on a molecule that controls the tightness of DNA that wraps around a protein that determines the composition of a gene. Imagine DNA is like a coil, and these proteins are like an axis. The tightness of the coil winding axis will affect the gene expression of the DNA. These molecules, called histone deacetylases (HDACs), are molecules that determine the tightness of DNA-wound proteins, such as high levels of HDAC enzymes in the human memory of the brains of patients with Alzheimer's syndrome. .

To further observe how this HDAC enzyme works, the team led by Hsiao-YingWey and Tonya Gilbert, researchers at the Harvard Medical School's biomedical imaging Martinos Centre, have spent seven years developing the chemical mixture. . This chemical mixture, called 11cMartinosatat, bound to the HDAC enzyme, shows which parts of the human brain will have HDAC enzymes, and how large the amount is.

The research was published in the journal Science Translational Medicine. In the study, researchers injected the chemical mixture into eight healthy individuals and used PET brain scanning to track the response. "This experiment demonstrates for the first time how the HDAC enzyme works in an active human brain," said Jacob Hooker, director of radiochemistry at Martino Center and co-author of the report.

A researcher at the Institute of Neurology of the Chinese Academy of Sciences, who is engaged in human brain imaging, told the reporter of the "First Financial Daily": "The idea of ​​using gene technology to judge gene expression has been around for ten years. The difference in this experiment is that it is on the one hand. On the other hand, PET imaging technology is used.” PET is considered to be the most advanced medical diagnostic technology at present. PET imaging system for small animals has been widely used in animal model research of diseases, new drug development and new treatment methods. Early research and early evaluation of efficacy, as well as basic biological research such as gene expression and cell tracking. Just last month, Yang Yongfeng, a researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, made a breakthrough in the high-resolution small animal PET prototype imaging system. But it is the first time PET has scanned humans to study gene expression.

The above researchers also questioned this experiment at Harvard Medical School: "The introduction of gene expression in the human body, just like genetic modification, is ethically appropriate to be confirmed. Because the input of foreign aid markers in the human body, if it does not affect Normal human metabolism is possible, and once it affects normal gene expression, or activates new gene expression, there is an ethic."

However, ethical concerns will not ultimately hinder the development of research. The results of the experiment have taken an important step toward the development of the booming epigenetics field. It also answers two eternal questions raised by human beings: "genetic or environmental?" (innate or acquired), that is, whether the changes in the human body are determined by genetic factors or environmental factors? Genetics give people the DNA's password, but the environment allows these DNA to be expressed differently. If you go back to the problem of DNA winding a protein like a thread, genetic epistemologists want to know how human diet and movement produce chemical changes in the human body by altering the tightness of DNA-wrapped proteins.

In the past, research in the field of human epigenetics was very scarce. This human brain imaging experiment provided at least some clues about how the environment and genes work together in the human body, so scientists are excited about the experimental results. A previous study showed that in the brains of schizophrenic patients, there were multiple link breaks between neurons. Today's study not only allows people to first observe epigenetic activity in active human brains, but this technology goes beyond previous mouse experiments and can be used for the diagnosis of diseases caused by brain disorders.

It is worth noting that in the experiment, the researchers also found that the morphology of this HDAC enzyme is more durable than expected, which also provides the possibility of further experiments for future human brain research.

How is the enzyme disrupted?

What scientists want to know more is how these long-lasting enzymes are disrupted. MiraJakovcevski, a psychiatric epigenetic researcher at the Max Planck Institute in Germany, said: "We have long known that this enzyme (HDAC) works in brain disorders such as depression or addiction. In the past, scientists have discovered through experiments that the levels of HDAC enzymes in the brain tissue of demented mental patients are abnormally high.

But past studies have not shown how HDAC enzymes work in human active brains. Because the brain tissue after death is usually stored for more than 12 hours, the HDAC enzyme changes rapidly after human death, so it is difficult to judge the performance in the living human brain with the results of the brain tissue of the dead. And scientists are only observing a part of the dead brain tissue. Nowadays, the scanning of the active human brain allows scientists to simultaneously observe the activity of any part of the human brain. Jakovcevski said: "This is very important for research. It can be observed how the enzymes in the active human brain are disrupted. And (relatively observing the brain tissue of the dead) is a very elegant way of studying."

Through this experiment, in addition to knowing the amount of HDAC enzyme in normal human brain, scientists have some amazing findings. First, the study found that this enzyme has little change when healthy people are resting, which is different from scientists' expectations, because the core voice in the field is the great difference in gene expression. In many cases in the past, human behavior and diet can change gene expression, such as riding a bicycle with only one foot in three months, or eating too much fat, which will affect the body's genes. Therefore, scientists believe that HDAC enzymes also show different levels in different parts of the human brain. At the same time, researchers found that the morphology of HDAC enzymes is the same in eight different parts of the human brain: whether it is the cerebellum that controls the human body with the highest HDAC content, or the brain-connected person with less enzyme content. Tissue whitematters. This makes scientists eager to find the answer to the next question: What is the link between HDAC enzymes and gene expression in these specific regions? Answering this question will help scientists better understand neurological diseases.

“Seeing” does not mean “reading”

Scientists believe that the level of HDAC is related to the degree of genetic change. The brain region with the highest HDAC content is also the brain region where the genes are least likely to change. Therefore, high levels of HDAC can impede human learning, even in normal human brains.

But this is not to say that the lower the content of HDAC, the better, because the genetic changes will cause other problems. Hooker, a professor of radiochemistry, and his team are demonstrating these hypotheses through experiments that scan the brains of animals.

Jakovcevski said: "The current technology may not be the most mature. We don't know how the level of HDAC affects the normal brain, such as how the brain's activity changes when people grow older. Even though researchers invented this The new 11cMartinosatat chemical mixture binds to three of the 11 HDAC enzymes known to humans, but this also means that other activities in the human brain are still unknown."

Professor Hooker said that observing active brain activity does not mean that scientists already understand how they work. "Visual presentation doesn't mean scientists understand how to interpret this signal," Professor Hooker said. "The biggest divide is that we found this abnormality in patients, but we don't know why."

Professor Hooker and his team's next step is to learn to discover abnormalities in patients and how they change in different situations. They have received funding to study the different manifestations of brain activity in patients with schizophrenia, Alzheimer's syndrome, and chorea. This means that the researchers will scan the brains of these patients to observe changes in the level of HDAC enzymes, and the resulting development of patient symptoms.

Previous studies have shown that preventing the production of HDAC can alleviate the condition of patients with Alzheimer's syndrome. But until now, there are still no neurological treatments for HDAC that have been approved by the US FDA, in part because people have not been able to prove the efficacy of the drug in the past, because it is difficult to visually show whether these drugs are really working, only by observing Changes in patient behavior to assess efficacy. “This kind of experiment is not convincing,” Professor Hooker said. “And by experimenting with the chemical mixture of 11cMartinosatat, scientists can directly understand whether the drug actually acts on the corresponding HDAC enzyme, which will help us in clinical trials. At the same time, we will further understand how the drug works and ultimately benefit the patient."

A researcher in the Institute of Neurology of the Chinese Academy of Sciences said that the "First Financial Daily" expressed "very interested" in this new technology. However, it remains to be seen how much value this technology will have for the research and early evaluation of drug discovery and new treatments.

Source: First Financial Daily