Parkinson’s disease treatments can help manage symptoms in the short term, but they often lead to long-term problems like dyskinesia, which causes uncontrollable movements.
Researchers at the University of Alabama at Birmingham (UAB) have found a new way to tackle this issue by treating dyskinesia as a “bad motor memory.”
In a study published in The Journal of Neuroscience, the UAB team discovered that blocking a protein called Activin A can stop dyskinesia symptoms and erase the brain’s “bad memory” response to certain Parkinson’s treatments.
“Instead of looking for a completely alternative treatment, we wanted to see if there was a way to prevent dyskinesia from developing in the first place,” explained Dr. David Figge, lead author and assistant professor at UAB.
Parkinson’s disease is a condition where neurons that produce dopamine die. To counter this, doctors use a drug called L-DOPA, which the body converts into dopamine.
While L-DOPA is effective in the short term, long-term use can lead to L-DOPA-induced dyskinesia. This condition causes involuntary movements like twitching, fidgeting, and head-bobbing.
Unfortunately, even if patients stop taking L-DOPA for a while, dyskinesia tends to return quickly once treatment resumes.
“It seemed like the brain was forming a motor memory,” said Dr. Karen Jaunarajs, assistant professor at UAB. “Each time a patient received L-DOPA treatment, this memory was recalled with every subsequent L-DOPA exposure.”
Due to the similarities between motor and behavioral memory, the researchers decided to treat dyskinesia like a bad memory. If they could make the brain forget its previous treatment history, they could extend the usefulness of L-DOPA for Parkinson’s patients.
The team first studied the striatum, a brain region crucial for motor control, to identify which cells were storing the “bad motor memory.” They found significant changes in neurons called D1-MSNs, which behaved similarly to neurons in the hippocampus during memory formation.
“We found that some of these D1-MSNs were activated by L-DOPA and expressed genes necessary for creating new connections with other cells,” Figge said. “This was very similar to what happens when you learn something new and recall that memory.”
One gene in these L-DOPA-activated neurons produces a protein called Activin A. By blocking Activin A, the researchers were able to prevent the development of L-DOPA-induced dyskinesia in mice.
“By prohibiting the protein from functioning, we were able to halt the development of dyskinesia symptoms in the mouse models, effectively erasing the brain’s memory of the motor response to L-DOPA,” Jaunarajs explained.
The ultimate goal is to find a way to block these bad motor memories completely, potentially eliminating dyskinesia symptoms in Parkinson’s patients. This discovery could lead to better long-term treatment options for those suffering from this neurodegenerative disease.
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