In the news – Schizophrenia, a chronic, neurological brain disorder, affects millions of people around the world. It causes a break between a person’s thoughts, feelings and behaviors. Symptoms include delusions, hallucinations, difficulty processing thoughts, and an overall lack of motivation. Patients with schizophrenia have a higher suicide rate and more health problems than the general population, and a lower life expectancy is lower.
There is no cure for schizophrenia, but the key to treating it more effectively is a better understanding of its origin. And that, according to Ryuta Mizutani, a professor of applied biochemistry at Tokai University in Japan, means studying the structure of brain tissue. In particular, it means comparing the brain tissue of people with schizophrenia and the tissue of people with good mental health, in order to see the differences as clearly as possible.
“There are only a few places in the world where you can conduct this research. Without 3D analysis of brain tissue this job would not be possible. “- Ryuta Mizutani, Professor, Tokai University
“The current treatment of schizophrenia is based on many hypotheses that we do not know how to confirm,” Mizutani said. “The first step is to analyze the brain and see how it is constituted differently.”
To do this, Mizutani and his colleagues from several international institutions collected eight small samples of brain tissue – four from healthy brains and four from samples from patients with schizophrenia, all collected post mortem – and brought them to a beam of 32-ID advanced photon Source ( APS), US Department of Energy Office Science Office staff at the DOE National Argonne Laboratory.
At APS, the team used powerful X-rays and high-resolution optics to capture three-dimensional images of these tissues. (Researchers collected similar images on the Super Photon Ring 8-GeV [SPring-8] light source in Japan.) The resolution of X-ray optics used on APS can be up to 10 nanometers. This is approximately 700 times less than the width of the average number of red blood cells, and those five cells have five drops of blood.
“There are only a few places in the world where you can conduct this research,” Mizutani said. “Without 3D analysis of brain tissue, this job would not be possible.”
According to Vincent De Andrade, a physicist in Argonna’s X-ray science department, taking high-resolution images is a challenge because the neurons being imaged can be inches long. A neuron is the basic working unit of the brain, a cell within the nervous system that transmits information to other cells to control bodily functions. The human brain has approximately 100 billion of these neurons, in a variety of sizes and shapes.
“The sample has to move through the X-ray beam in order for the neurons to follow through the sample,” De Andrade explained. “The field of view of our X-ray microscope is about 50 microns, about the width of a human hair, and you have to track those neurons a few millimeters.”
These images showed that the structures of these neurons differ uniquely in each patient with schizophrenia, which Mizutani said is evidence that the disease is associated with these structures. The images of healthy neurons were relatively similar, while the neurons of patients with schizophrenia showed far greater deviations, both from the healthy brain and from each other.
More studies are needed, Mizutani said, to determine exactly how neuronal structures are linked to the onset of the disease and to devise a treatment that can alleviate the effects of schizophrenia. As X-ray technology continues to improve – APS, for example, needs to undergo a massive upgrade that will increase its brightness by up to 500 times – so will the opportunities for neuroscientists.
“Upgrading the APS will provide better sensitivity and resolution for imaging, making the process of mapping neurons in the brain faster and more accurate,” De Andrade said. “We would need resolutions larger than 10 nanometers to capture synaptic connections, which is the holy grail of comprehensive neuronal mapping, and they should be achieved by upgrading.”
De Andrade also noted that while electron microscopy is used to map the brains of small animals – for example, fruit flies – this technique would take a long time to image the brains of larger animals, such as mice, let alone fill the human brain. Extremely bright high-energy rays like those on the APS, he said, could speed up the process, and advances in technology will help scientists gain a more complete picture of brain tissue.
For neuroscientists like Mizutani, the ultimate goal is fewer people suffering from brain diseases like schizophrenia.
“Differences in brain structure between healthy and schizophrenic people must be linked to mental disorders,” he said. “We need to find a way to make people healthy.”
Mizutani and his team reported their results in translational psychiatry.
About an advanced photon source
The U.S. Department of Energy’s Advanced Photon Source (APS) at Argonne National Laboratory is one of the world’s most productive X-ray plants. APS provides high-brightness X-rays to a diverse community of researchers in materials science, chemistry, condensed matter physics, life and environmental sciences, and applied research. These X-rays are ideal for researching materials and biological structures; distribution of elements; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injection sprays, which are all the foundations of the economic, technological and physical well-being of our state. Each year, more than 5,000 researchers use APS to produce over 2,000 publications detailing important discoveries and solving more vital biological protein structures than users of any other X-ray research facility. APS scientists and engineers are innovating technology that is at the heart of improving the performance of accelerators and light sources. These include inserts that produce X-rays of extreme brightness that have been appreciated by researchers, lenses that focus X-rays at several nanometers, instrumentation that maximizes the way X-rays communicate with the samples being studied, and software that collects and manages vast amounts of data. from research discoveries at APS.
In this research, the resources of Advanced Photon Source, the American DOE Office of Science, the Office of Science, which was managed for the DOE Office of Science by the Argonne National Laboratory under contract no. DE-AC02-06CH11357.
Argonne National Laboratory seeks solutions to burning national problems in science and technology. The country’s first national laboratory, Argonne, conducts leading basic and applied scientific research in almost every scientific discipline. Argona researchers are working closely with researchers from hundreds of companies, universities and federal, state and municipal agencies to help them solve their specific problems, advance American scientific leadership and prepare the nation for a better future. With employees from more than 60 countries, Argonne is managed by UChicago Argonne, LLC, for the Office of Science of the U.S. Department of Energy.
U.S. Department of Energy Office of Science is the greatest proponent of basic physical science research in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.