The link between Parkinson’s gene and vocal problems can lead to early diagnosis

Summary: A specific gene for Parkinson’s disease may be the driver behind sound-related problems. Studies show that it can lead to early diagnosis and treatment of Parkinson’s disease.

A source: University of Arizona

Parkinson’s disease is known for its motion-related symptoms, especially tremors and stiffness.

However, it is also known that Parkinson’s disease can interfere with speech. Studies show that these symptoms usually appear long before the onset of the disease, sometimes decades before the onset of movement-related symptoms.

New research by neurologists at the University of Arizona suggests that a specific gene associated with Parkinson’s disease may be behind this sound-related problem – helping to diagnose and treat Parkinson’s patients early.

Julie E., assistant professor of neurology and speech, language and hearing at the College of Research. Conducted in Miller’s laboratory.

“We have a big gap here – we don’t know how this disease affects the brain areas to produce sound, and it’s really an opportunity to intervene early and find a better treatment,” Miller said. He is a member of the Department of Neurology and the Interdisciplinary Program in Neuroscience, and the UArizona BIO5 Institute.

The study was published in a scientific journal on Wednesday PLOS ONE. Cesar A. Medina, former Candidate of Philosophical Sciences. A student in Miller’s lab and now a doctoral student at Johns Hopkins University, he is the co-author of the paper.

The study also involved former UAE student Eddie Vargas, who recently visited Tucson College of Medicine, and Stephanie Munger, a research specialist in the Department of Neurology.

A unique, ideal model for the study of human speech

To find out if the Parkinson’s gene, called alpha-synuclein, is related to sound changes, researchers turned to singing birds from Australia.

Birds are an ideal role model for human speech and sound for a number of reasons, Medina said. Young birds learn their songs from adult males, just like their parents, and babies learn to listen to their parents. The part of the brain that deals with speech and language is organized in a very similar way to the human brain.

“These similarities in behavior, anatomy and genetics allow zebra fins to be used as role models for human speech and voice,” Medina said.

To find out how alpha-synuclein affects the sound of birds, researchers first obtained basic recordings of their songs. They then introduced a copy of the gene into some of the birds; The researchers did not assign genes to other birds to compare the results. The songs of all the birds were recorded immediately after the introduction of the gene, and then one, two, or three months later.

Using a computer program, the researchers analyzed and compared the acoustic features of the songs over time, studied the pitch, amplitude, and duration of the songs, and determined when the birds’ voices changed.

Preliminary findings have shown that alpha-synuclein affects song production. Image in public domain

Preliminary findings have shown that alpha-synuclein affects song production. Birds with the gene sing less after two months, and sing less at the beginning of the song session three months after receiving the gene. The voices were also softer and shorter, as was the case with human disease.

Another step to early diagnosis and treatment

To determine if the effects of speech are related to changes in the brain, the researchers studied a part of the brain called the X-region. They found that the X region was high in alpha-synuclein protein. The gene actually caused changes in the brain that led to changes in sound output, Medina said.

This connection, he added, was predicted in previous studies by Parkinson’s, but it is not conclusive.

The next step, Miller said, is to determine how to apply these findings to human data, which could provide more answers that could lead to improved Parkinson’s diagnosis and treatment – before motion-related symptoms tell the patient to see a neurologist.

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This indicates a hand covered with electrodes

Miller’s long-term goal, he said, is to partner with other researchers and private companies to develop drugs that target alpha-synuclein and other Parkinson-related genes.

By doing so, Medina said, “we can stop the development of Parkinson’s disease before it adversely affects the patient’s quality of life.”

News about genetics and Parkinson’s disease research

Author: Press service
A source: University of Arizona
The connection: Press Service – University of Arizona
Photo: Image in public domain

Original study: Open access.
“Vocal changes in the zebra finch model of Parkinson’s disease are characterized by excessive expression of alpha-synuclein in the anterior cerebral pathway dedicated to song,” César A. Medina et al. PLOS ONE


Abstract

Vocal changes in the zebra finch model of Parkinson’s disease are characterized by alpha-synnuclein expression in the anterior cerebral pathway dedicated to the song.

Deterioration of human voice and speech quality is the first sign of Parkinson’s disease (PD). In humans, the neural circuit that supports the control of the sound motor consists of the cortico-basal ganglia-thalamo-cortico cycle. The areas of the basal ganglia in this cycle, the striatum and the globus pallidus, play a role in modulating acoustic features of sound behavior, such as loudness, pitch, and articulatory speed. In PD, this area is involved in pathogenesis.

In PD animal models, the accumulation of toxic aggregates in the midbrain and striatum, including the neural alpha-synuclein (αsyn) protein, leads to impaired leg and voice movement. In rodent models, the study of sound disorders was difficult due to the lack of clearly defined cortico-basal ganglia schemes for sound production. In addition, the deterioration of sound quality at the beginning of PD is a direct result of αsyn-induced neuropathology.

Here, we use the well-characterized vocal schemes of an adult male zebra finch to experimentally target a song pathway, anterior forebrain, using an adeno-associated virus that represents a wild-type human αsin gene. SNCA. We found that the over-expression of αsyne in this way coincided with higher levels of insoluble, monomeric αsine compared to control flies.

In addition to the short and low-quality syllables, which are the most important unit of the song, flaws in the song’s composition have also been identified. These sound changes are similar to the sound anomalies observed in people with PD.

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