Exploring New Types of Parkinson's-affected Neurons to Expand Treatment Opportunities
In Parkinson’s disease (PD), dopamine-releasing neurons in the brain region called the
substantia nigra break down over time. These neurons play important roles in regulating the
activity of other neurons in the motor region of the cerebral cortex, so their progressive loss
leads to the movement symptoms seen in the disease. While a great deal of PD research has
looked into the disease’s impact on the basal ganglia, less is known about the cellular changes
that happen to the motor cortex. To better understand these downstream neurological effects and how to better treat or prevent them clinically, Hong-yuan Chu, PhD, recipient of a
Parkinson’s Foundation 2023 Bill and Amy Gurley Impact Award, will be doing a deep-dive into
the chemical and functional changes that occur in motor cortex neurons after substantia nigra dopamine neurons are lost.
From his lab at the Van Andel Research Institute in Grand Rapids, Michigan, Dr. Chu has identified a specific type of neuron in the motor cortex called parvalbumin-expression interneurons (PV-INs) that seem to become more sensitive and overreactive after PD-like dopamine neuron loss. Using mouse models, Dr. Chu and his team will use sophisticated electrophysiology recording techniques to measure how differently PV-INs act in PD and non-PD contexts.
With a better understanding of how PV-INs change during PD progression, Dr. Chu will next test how well those neurons interact with other neurons with and without dopamine neurons present. PV-INs primarily communicate with pyramidal tract neurons (PTNs), which relay signals to the spinal cord that get forwarded to muscles for movement. With powerful microscopes, Dr. Chu will be able to see how PV-INs organize themselves around PTNs to help facilitate motor signaling, comparing their effectiveness in mice with and without PD-like dopamine neuron loss.
Completing this research will provide exciting new data on a relatively understudied type of neuron in the context of PD. Through these experiments, Dr. Chu hopes to find new targets for treatment in the brain, opening up additional therapeutic options in the future. After learning that he had received this award, Dr. Chu said: “I am grateful for the support of the Parkinson’s Foundation, which will help my lab pursue new ideas and accelerate expansion of our research program. This work has great potential to provide new insights into how Parkinson’s affects brain function, which can help us design better treatments in the future.”
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