Researchers find link between Parkinson's gene and vocal issues that
could lead to earlier diagnosis

Date:
May 4, 2022
Source:
University of Arizona
Summary:
Neuroscientists found that higher levels of the alpha-synuclein
protein in the brain can lead to changes in vocal production.



FULL STORY ========================================================================== Parkinson's disease is perhaps best known for its movement-related
symptoms, particularly tremors and stiffness.


==========================================================================
But the disease is also known to hinder vocal production, giving those
with Parkinson's a soft monotonous voice. Those symptoms, research has suggested, often appear much earlier in the disease's development --
sometimes decades before movement-related symptoms.

New research by University of Arizona neuroscientists suggests that
a specific gene commonly associated with Parkinson's may be behind
those vocal-related issues -- a finding that could help lead to earlier diagnoses and treatments for Parkinson's patients.

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

"We have this big gap here -- we don't know how this disease impacts the
brain regions for vocal production, and this is really an opportunity
to intervene early and come up with better treatments," said Miller,
who also has joint appointments in the Department of Neurology and the
Graduate Interdisciplinary Program in Neuroscience, and is a member of
the UArizona BIO5 Institute.

The study was published Wednesday in the scientific journal PLOS
ONE. Ce'sar A.

Medina, a former Ph.D. student in Miller's lab who is now a postdoctoral scholar at Johns Hopkins University, is the paper's lead author. Also
involved in the research were Eddie Vargas, a former UArizona
undergraduate student who will soon attend the College of Medicine --
Tucson, and Stephanie Munger, a research professional in the Department
of Neuroscience.



==========================================================================
A unique, ideal model for studying human speech To investigate any
correlation between vocal changes and the Parkinson's- related gene --
known as alpha-synuclein -- the researchers turned to the zebra finch,
a songbird native to Australia.

The birds are an ideal model for human speech and voice pathways for
several reasons, Medina said. Young finches learn their songs from older, father-like male birds, much in the same way babies learn to speak 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 across behavior, anatomy and genetics allow us to
use the zebra finches as a model for human speech and voice," Medina said.

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



==========================================================================
The researchers used computer software to analyze and compare the
acoustic features of the songs over time, studying pitch, amplitude
and duration of the songs to determine whether and when the birds'
vocal production changed.

Initial findings showed that alpha-synuclein did affect song
production. The birds with the gene sang less after two months, and they
sang less at the start of a song session three months after receiving the
gene. The vocalizations were also softer and shorter, findings similar
to what is seen in the human disease.

Another step toward earlier diagnoses and treatments To determine
whether the effects on speech were connected to changes in the brain,
the researchers zeroed in on a section of the brain called Area X. They
found that there were higher levels of the alpha-synuclein protein in
Area X, helping them establish that the gene did, in fact, cause the
changes in the brain that led to changes in vocal production, Medina said.

This connection, he added, had been predicted in previous Parkinson's
research, but it was not conclusive.

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
Parkinson's diagnoses and treatments -- ones that come long before movement-related symptoms tell a patient to visit a neurologist.

The long-term goal of the Miller Lab, 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.

Doing so, Medina said, would mean "we could stop the progression of
Parkinson's disease before it becomes a detrimental impediment to the
quality of life for the patient."

========================================================================== Story Source: Materials provided by University_of_Arizona. Original
written by Kyle Mittan.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Cesar A. Medina, Eddie Vargas, Stephanie J. Munger, Julie E. Miller.

Vocal changes in a zebra finch model of Parkinson's disease
characterized by alpha-synuclein overexpression in the
song-dedicated anterior forebrain pathway. PLOS ONE, 2022; 17 (5):
e0265604 DOI: 10.1371/ journal.pone.0265604 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/05/220504144523.htm

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