By capturing details of brain cells at the nanometer scale, researchers have found evidence that the neurons of people with schizophrenia could have unique differences in thickness and curvature, and this could even explain some of their symptoms.
The finding comes from the analysis of only a small handful of donors and goes a long way in demonstrating how contrasting nerve cell structures can explain neurological status.
But as we grow our understanding of these unusual features, it could lead to better treatment methods, which would help provide millions of people around the world with a better quality of life.
The study, led by researchers at Tokai University in Japan, made use of two different X-ray microscope technologies, one at the SPring-8 light source in Japan, and the other at the advanced photon source ( APS) from the US Department of Energy.
Both accelerate the particles along the curved paths in what is known as the synchrotron, causing them to emit short wavelengths of electromagnetic radiation into the part of the X-ray spectrum.
Using X-rays as a source of radiation to photograph fine details of tiny objects, such as neurons, can be a double-edged sword.
On the one hand, their narrow wavelengths are only those that capture each buckle and tissue of a cell’s membrane. APS is capable of achieving a resolution of up to 10 nanometers, a scale that brings it remarkably close to revealing the texture of the individual protein channels that dot a cell membrane.
Seen from enough angles, it is possible to reconstruct neurons as high-definition three-dimensional terrain.
Unfortunately, no matter how small the neurons are, they are also quite long. Tracing every bump on its surface is a tedious job when you have to crawl along whole millimeters of your body.
“The sample has to move through the X-ray beam to track the neurons through the sample,” says Vincent De Andrade, a physicist in Argonne’s X-ray scientific division.
“The field of view of our X-ray microscope is about 50 microns, about the width of a human hair, and you have to follow these neurons for several millimeters.”
Taking tissue samples from a selective part of the brain in four dead individuals diagnosed with schizophrenia and four without, the team undertook the tedious task of scanning nerve cells using the two different synchrotron facilities.
The images were combined to reconstruct the neurons as digital models, which contributed to a larger data set that could be compared and statistically contrasted in search of distinctive features.
They found, statistically speaking, that the thickness and curvature of cellular features extending away from the body of the neuron were significantly different among individuals with schizophrenia, compared with those who did not.
These variations could affect the way neurons transmit messages by their length, which could help explain the characteristics of the disorder, which in its most severe forms includes hallucinations, impaired motor control, and delusions.
Exactly what is behind these deviations in cell geometry or whether the variations extend to the synaptic “toes” of the neuron will require even more detail than the generation synchrotrons can handle. current.
That could change when APS gets a $ 815 million upgrade in the next few years that will produce it with X-ray beams 500 times brighter than the ones it currently emits.
“The APS update will allow for better sensitivity and resolution of the image, which will make the process of mapping neurons in the brain faster and more accurate,” says De Andrade.
“We would need resolutions above 10 nanometers to capture synaptic connections, which is the holy grail for a complete mapping of neurons, and these should be achievable with the upgrade.”
Bringing together the mechanisms of schizophrenia development is a complex process that will require advanced imaging and computing technology.
Gradually we come to understand the multitude of genetic and environmental factors that see the brain change while in the womb and continue to change as the child grows into adulthood.
If there are ways to detect it and treat it early, we could help limit, if not prevent, the worst of the traits that can put people at risk for serious mental illness.
This research was published in Translational psychiatry.