Link between Parkinson’s gene and voice problems could lead to earlier diagnosis

Summary: A specific gene linked to Parkinson’s disease may be at the root of the speech production problems associated with the disease. The findings could lead to earlier diagnosis and treatment of Parkinson’s disease.

Source: University of Arizona

Parkinson’s disease is perhaps best known for its movement-related symptoms, particularly tremors and stiffness.

But the condition is also known to hamper vocal production, giving people with Parkinson’s a soft, monotonous voice. These symptoms, according to research, often appear much earlier in the development of the disease, sometimes decades before movement-related symptoms.

New research from neuroscientists at the University of Arizona suggests that a specific gene commonly associated with Parkinson’s disease may be to blame for these voice-related problems, a finding that could help lead to diagnosis and earlier treatment for patients with Parkinson’s disease.

The research was conducted in the lab of Julie E. Miller, assistant professor of neuroscience and speech, language, and hearing sciences at the College of Science.

“We have this big gap here – we don’t know how this disease affects regions of the brain for speech production, and this is really an opportunity to intervene early and come up with better treatments,” said Miller, who has also cross appointments in the Department of Neurology and the Interdisciplinary Neuroscience Graduate Program, and is a Fellow of the UArizona BIO5 Institute.

The study was published Wednesday in the scientific journal PLOS ONE. César A. Medina, a former Ph.D. student in Miller’s lab who is now a postdoctoral fellow at Johns Hopkins University, is the paper’s senior author.

Eddie Vargas, a former UArizona undergraduate who will soon be attending the College of Medicine in Tucson, and Stephanie Munger, a research professional in the Department of Neuroscience, also participated in the research.

A unique and ideal model for studying human speech

To investigate any correlation between vocal changes and the gene linked to Parkinson’s disease, known as alpha-synuclein, the researchers turned to the zebra finch, a songbird native to Australia.

Birds are an ideal model for human speech and vocal pathways for several reasons, Medina said. Young finches learn their songs from older, father-like male birds, the same way babies learn to talk by listening to their parents. The part of a finch’s brain that deals with speech and language is also organized very similarly to its counterpart in the human brain.

“These similarities between behavior, anatomy, and genetics allow us to use zebra finches as a model for human speech and voice,” Medina said.

To see how alpha-synuclein might affect vocal production in birds, the researchers first took baseline recordings of their songs. They then introduced a copy of the gene into some of the birds; other birds did not receive the gene so the researchers could compare the results. All bird songs were re-recorded immediately after gene introduction, then one, two and three months later.

The researchers used computer software to analyze and compare the acoustic characteristics of the songs over time, studying the pitch, amplitude and duration of the songs to determine if and when the birds’ vocal production changed.

Early results showed that alpha-synuclein affected song production. Image is in public domain

Early results showed that alpha-synuclein affected song production. Birds carrying the gene sang less after two months, and they sang less at the start of a singing session three months after receiving the gene. Vocalizations were also softer and shorter, findings similar to what is seen in human disease.

A step closer to earlier diagnosis and treatment

To determine if the effects on speech were related to changes in the brain, the researchers focused on a section of the brain called the X-zone. They found that there were higher levels of the protein alpha-synuclein in the zone X, which helped them establish that the gene did, in fact, cause the changes in the brain that led to changes in voice output, Medina said.

This connection, he added, had been predicted in previous research on Parkinson’s disease, but it was inconclusive.

The next step, Miller said, is figuring out how to apply these findings to human data, which could provide more answers that lead to better diagnoses and treatments for Parkinson’s disease — those that occur long before the symptoms associated with the disease. movement does require a patient to see a neurologist.

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The Miller Lab’s long-term goal, she said, is to partner with other researchers and private companies to develop drugs that target alpha-synuclein and other genes associated with Parkinson’s disease.

This, Medina said, would mean “we could stop the progression of Parkinson’s disease before it becomes a detrimental obstacle to the patient’s quality of life.”

About this research news on genetics and Parkinson’s disease

Author: Press office
Source: University of Arizona
Contact: Press Office – University of Arizona
Picture: Image is in public domain

Original research: Free access.
Vocal changes in a zebra finch model of Parkinson’s disease characterized by overexpression of alpha-synuclein in the anterior forebrain vocal pathwayby César A. Medina et al. PLOS ONE


Vocal changes in a zebra finch model of Parkinson’s disease characterized by overexpression of alpha-synuclein in the anterior forebrain vocal pathway

Deterioration in a person’s voice and speech quality is an early marker of Parkinson’s disease (PD). In humans, the neural circuit that supports vocal motor control consists of a cortico-basal ganglia-thalamo-cortico loop. The regions of the basal ganglia, striatum and globus pallidus, in this loop play a role in modulating the acoustic characteristics of vocal behavior such as volume, pitch and articulatory rate. In PD, this area is involved in the pathogenesis.

In animal models of PD, the accumulation of toxic aggregates containing the neuronal protein alpha-synuclein (αsyn) in the midbrain and striatum leads to motor impairments in limbs and voice. It has been difficult to study vocal impairments given the lack of well-defined corticobasal ganglia circuitry for vocalization in rodent models. Moreover, it is not yet clear whether the deterioration of voice quality in early PD is a direct result of αsyn-induced neuropathology.

Here, we take advantage of the well-characterized vocal circuits of the adult male zebra finch songbird to experimentally target a dedicated song pathway, the anterior forebrain pathway, using an adeno-associated virus expressing the human wild-type αsyn gene, SNCA. We found that overexpression of αsyn in this pathway coincides with higher levels of insoluble monomeric αsyn compared to control finches.

Deficiencies in song production were also detected as well as shorter and lower quality syllables, which are the basic unit of song. These voice changes are similar to the voice abnormalities seen in people with PD.

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