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By capturing the details of brain cells at the nanoscale, the researchers found evidence that the neurons of people with schizophrenia may have unique differences in thickness and curvature, which may even explain some of their symptoms.
The finding comes from an analysis on a small handful of donors and falls short of demonstrating how contrasting nerve cell structures could explain neurological disease.
But as our understanding of these unusual characteristics grows, it could lead to better methods of treatment, helping to give tens of millions of people around the world a better quality of life.
The study, led by researchers at Tokai University in Japan, used two different x-ray microscope technologies, one at the SPring-8 light source installation in Japan, the other at the source. US Department of Energy Photon Advanced (APS).
Both of these accelerate particles along curved paths in what’s called a synchrotron, causing them to reject short wavelengths of electromagnetic radiation in the x-ray portion of the spectrum.
Using x-rays as a radiation source to photograph small details of tiny objects – such as neurons – can be a bit of a double-edged sword.
For one thing, their tight wavelengths are just what it takes to capture every loop and weave of a cell’s membrane. APS is capable of resolution of up to 10 nanometers, a scale that brings it remarkably close to revealing the texture of individual protein channels dotting a cell membrane.
Seen from enough angles, it is possible to reconstruct neurons in the form of high-definition three-dimensional terrains.
Unfortunately, however small the neurons are, they are also quite long. Tracing every bump on their surface is a tedious job when you have to weave your way through whole millimeters of their body.
“The sample has to move through the x-ray beam to trace the neurons through the sample,” explains Vincent De Andrade, physicist in the X-ray Science division of Argonne.
“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 selected part of the brain from four deceased people diagnosed with schizophrenia, and four without, the team undertook the tedious job of scanning nerve cells using the two different synchrotron facilities.
The images were combined to reconstruct neurons as digital models, which contributed to a larger data set that could be statistically compared and contrasted for distinguishing features.
They found, statistically speaking, that the thickness and curvature of cellular features extending away from the neuron body were significantly different among people with schizophrenia, compared to those without the disease.
These variations could affect the way neurons carry messages along their entire length, which could partly explain the characteristics of the disorder, which in its most severe forms includes hallucinations, impaired motor control and delusions.
What exactly lies behind such deviations in cell geometry, or whether the variations extend to the synaptic “toes” of the neuron, will require even more detail than current generation synchrotrons can handle.
That could change when APS gets an $ 815 million upgrade over the next few years, which will see it produce x-ray beams far 500 times brighter than those it currently emits.
“Upgrading the PSA will allow better sensitivity and resolution for imaging, making the process of mapping neurons in the brain faster and more accurate,” says De Andrade.
“We would need resolutions greater than 10 nanometers to capture synaptic connections, which is the holy grail for complete neural mapping, and these should be achievable with the upgrade.”
Putting together the mechanisms behind the development of schizophrenia is a complex process that will require advanced imaging and computational technology.
We are gradually coming to understand the multitude of genetic and environmental factors that see the brain change while it is still in the womb, and continue to change as a child grows into adulthood.
If there are ways to detect and treat this disease early, we could help limit, if not prevent, the worst traits that can put people at risk for serious mental illness.
This research was published in Translational psychiatry.
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