Erasing "Bad Memories" to Prolong Parkinson's Treatment Effectiveness
Common treatments for Parkinsons disease can alleviate short-term symptoms but often lead to long-term issues, such as dyskinesia, characterized by uncontrollable movements and postures ().
In a recent study published in The Journal of Neuroscience, researchers at the University of Alabama at Birmingham explored a novel approach to dyskinesia by treating it as a "bad motor memory." They discovered that blocking a protein called Activin A could stop dyskinesia symptoms and effectively erase the brain's "bad memory" response to certain Parkinson's treatments.
‘Blocking Activin A halts dyskinesia in Parkinson's, erasing motor memory of L-DOPA response. #medindia #parkinsons’
Preventing Dyskinesia: A New Approach to Long-Term Parkinson's Treatment
"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," said David Figge, M.D., Ph.D., lead study author and assistant professor in the UAB Department of Pathology. "If dyskinesia does not occur, then patients could potentially stay on their Parkinson's treatment for longer."Parkinson's disease is a neurodegenerative disorder caused by the death of neurons that make dopamine. To counteract this loss, clinicians currently use L-DOPA, a drug that is a precursor to dopamine.
Short term, L-DOPA is helpful; but long term, it leads to L-DOPA-induced dyskinesia in some patients, which causes involuntary, erratic movements such as twitching, fidgeting, head-bobbing or body swaying. Even if a patient stops taking L-DOPA for a certain period, dyskinesia has proved to come back quickly - as soon as these patients restart treatment.
"It seemed like the brain was forming a motor memory, and each time a patient received L-DOPA treatment, this memory then recalled upon every subsequent L-DOPA exposure," said Karen Jaunarajs, Ph.D., assistant professor in the UAB Department of Neurology.
Motor Memory in Parkinson's Disease: Insights from Striatal Neurons
Due to the overlaps between motor and behavioral memory, the team decided to approach dyskinesia like a bad memory. If they could find a way to cause the brain to forget its previous treatment history, they could potentially prolong the usefulness of L-DOPA for Parkinson's treatment.Researchers first studied the striatum, the brain region significant to motor control, to figure out which cells were storing the "bad motor memory." The most significant changes observed were in neurons called D1-MSNs, which acted in a similar way to neurons in the hippocampus when it is forming a memory.
"We found that some of these D1-MSNs were expressing genes indicating that they were being activated by L-DOPA and genes that were 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."
Researchers found that one gene in these L-DOPA-activated D1-MSN neurons is translated into a protein called Activin A. By blocking the function of Activin A, researchers were able to block the development of L-DOPA-induced dyskinesia in mouse models.
"In essence, 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 said.
Ultimately, the hope is that these findings will lead to an understanding of how to block these bad motor memories altogether - eradicating dyskinesia-related symptoms in Parkinson's patients.
Reference:
- Erasing "bad memories" to improve long term Parkinson's disease treatment - (https:www.uab.edu/news/research/item/14239-erasing-bad-memories-to-improve-long-term-parkinson-s-disease-treatment)
Source: Eurekalert