MJFF funding novel study of anxiety mechanisms in Parkinson’s
Project focusing on alpha-synuclein buildup in key brain region
A research grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) will support a new study that’s investigating the biological mechanisms underlying anxiety as a symptom of Parkinson’s disease.
Titled “Investigating the Mechanisms of Alpha-synuclein-induced Anxiety in a Novel Preclinical Model of Parkinson’s Disease,” the project will explore whether the accumulation of alpha-synuclein — a protein strongly linked to Parkinson’s development — in a brain region called the amygdala contributes to anxiety development. This brain region is critical for processing emotional and sensory responses, such as fear, anxiety, and aggression.
The project brings together leading researchers from opposite sides of the U.S. It will be led by Christopher Bishop, PhD, in collaboration with Marvin Diaz, PhD, at Binghamton University in New York, alongside Fredric Manfredsson, PhD, at the Barrow Neurological Institute in Arizona.
“We have evidence from clinical pathology as well as some unique features of anxiety to suggest that it is organic and not simply a perception driven by disease diagnosis,” Bishop said in a university news story detailing the work.
Parkinson’s is caused by the dysfunction and loss of dopaminergic neurons, the nerve cells that produce dopamine, a neurotransmitter essential for motor control. This occurs mainly in a brain region called the substantia nigra, and it triggers the hallmark motor symptoms of the disease.
The toxic buildup of alpha-synuclein may also impact the amygdala, according to the researchers, potentially disrupting emotional processing and contributing to nonmotor symptoms such as anxiety. Such symptoms often appear before motor impairments.
Investigating how anxiety emerges as a Parkinson’s symptom
“Although Parkinson’s disease (PD) is known as a movement disorder, nonmotor symptoms like anxiety can severely reduce individuals’ quality of life,” a study rationale on the MJFF’s website states.
In this newly funded project, the researchers aim to determine whether alpha-synuclein accumulation disrupts amygdala function, leading to anxiety. To investigate this, the team will use a novel preclinical model developed in Manfredsson’s lab, which overexpresses human alpha-synuclein.
“[Diaz] knows the connectivity of the amygdala very well. We saw that as a perfect marriage with our project because Parkinson’s patients display pathology in the amygdala fairly early on,” Bishop said. “That led us to believe that this was a place that needs a closer look.”
Using this model, the researchers will monitor how anxiety emerges over the course of disease progression. They also aim to identify brain regions, including the amygdala, that may drive these changes. As one example, examining rodent behavior in novel environments will help assess anxiety levels — less exploratory behavior typically signals heightened anxiety, the team noted.
This work will be coupled with biomarker studies, such as detecting alpha-synuclein in cerebrospinal fluid, the liquid that surrounds the brain and spinal cord. Altogether, according to the team, the research could lead to earlier diagnosis and the development of treatments that prevent or slow disease progression.
Understanding this pathology [cause] and its effects on behavior will not only advance scientific knowledge, but also identify new ways to diagnose and treat people with [Parkinson’s disease].
Initial experiments led by senior graduate student Natalie Lipari have already shown that anxiety behaviors and functional disruption occur in the amygdala in this model, without evident neuron loss.
“That means two things: If they’re not degenerating, those cells are still available; they’re just not working as they should,” Bishop said. “The upside of that is because they’re still there, we may be able to modulate them with treatment.”
According to the study rationale, “understanding this pathology [cause] and its effects on behavior will not only advance scientific knowledge, but also identify new ways to diagnose and treat people with PD.”
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