By Michelle Jaffee
New research by MBI neuroscientists suggests that well before classic symptoms of Parkinson’s disease appear, activity of dopamine neurons in the substantia nigra — a brain region affected in the progressive movement disorder — is already altered. These findings could open a critical window for early intervention.
Published July 11 in the journal npj Parkinson’s Disease, the mouse-model study reveals a paradox: that while the protein a-synuclein disrupts dopamine-producing cells in one midbrain region, they remain mostly intact in a neighboring one. This finding illuminates processes that drive neuronal degeneration in Parkinson’s, the researchers reported.
“We caught the disease in the act, at the moment when neurons are malfunctioning but not yet dead,” said lead author Leah Phan, a doctoral student in the lab of Habibeh Khoshbouei, Pharm.D., Ph.D. “That window gives us a valuable opportunity to intervene early.”
Parkinson’s symptoms, which can include problems with balance, stiffness and slowness, typically begin after a significant loss of dopamine neurons in the substantia nigra, the researchers said.
“Understanding the earliest functional breakdown of dopamine neurons helps us design drugs or gene therapies aimed at restoring healthy firing patterns and network connectivity before irreversible damage occurs,” said Khoshbouei, a UF professor of neuroscience and psychiatry.
The study used electrophysiology, histology and high-speed calcium imaging to map real-time network connectivity.
Next, the research team will focus on understanding how long it takes for stressed networks in the substantia nigra to degenerate. They also plan to analyze side-by-side comparisons of the substantia nigra and neighboring ventral tegmental area, where dopamine neurons show resilience, to identify any “molecular shields” that could offer protection by slowing or preventing loss of dopamine neurons.