Specific changes in brain pathways may counteract genetic mutations for the movement disorder dystonia, according to new research in the August 5 issue of The Journal of Neuroscience.
Few people who inherit dystonia genes display symptoms — namely sustained muscle contractions and involuntary gestures — and the study provides a possible explanation. This result could lead to new treatments for the estimated 500,000 North Americans diagnosed with dystonia.
In this study, researchers looked for the first time at how brain connections might explain the disorder. "Our findings begin to show why someone can live with a genetic mutation without ever developing the disease," said David Eidelberg, MD, at The Feinstein Institute for Medical Research, the study's senior author.
Scientists at The Feinstein Institute used an MRI-based approach called diffusion tensor imaging, a technique that maps the connections between structures in the human brain. Twenty patients with mutated genes associated with dystonia were assessed (12 with symptoms, eight without), along with eight healthy patients without these mutations.
The authors identified two different brain pathways that determine the severity of symptoms. One pathway connecting the cerebellum with the thalamus is abnormal in all people carrying the mutant gene, and predisposes carriers to dystonia. In the patients with mutated genes but no symptoms, a second pathway between the thalamus and the cortex is also abnormal. Surprisingly, this second pathway is normal in patients with symptoms. The researchers suggest that in people who have the mutations but no symptoms, the second abnormality may offset the effect of the first, preventing the disease's outward signs.
David Standaert, MD, PhD, at University of Alabama at Birmingham, is an expert in Parkinson's disease and other movement disorders and was not affiliated with the study. Standaert says that although dystonia is a relatively rare disorder, the study has implications for other neurological illnesses, such as Parkinson's, Alzheimer's, and Huntington's diseases; ataxia and muscular dystrophies; and even forms of migraine.
"The core idea here is that many diseases can be triggered by a single gene, but the expression of this gene can differ greatly, even in individuals from the same family," Standaert said. "Dystonia provides dramatic examples of this. Two siblings may have the same abnormal gene, but one will be severely disabled by twisting and cramping of the muscles, while the other will be essentially normal."
The pathway abnormalities identified in the study could likely have formed in an early stage of brain development, Standaert suggested. Symptoms in adult life, therefore, may be determined by subtle shifts in early brain growth. Detailed study of these newly implicated pathways in both humans and animals could lead to ways to prevent symptoms, if balance to the affected pathways is restored.
The research was supported by the National Institutes of Health, the Bachmann-Strauss Dystonia and Parkinson Foundation, and the General Clinical Research Center of The Feinstein Institute for Medical Research.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system. Eidelberg can be reached at email@example.com .
Kat Snodgrass | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy