Interesting Article about dyskinesia
Researchers Discover Brain Circuit Underlying Dyskinesia in PD It has long been thought that dyskinesias — the involuntary movements that are experienced by many people who live with Parkinson’s disease (PD) — are caused by the long-term use of levodopa (Sinemet®). But research funded by the Parkinson’s Disease Foundation (PDF) and published on September 2 in Neuron has uncovered new answers about this debilitating aspect of the disease. Researchers working under the direction of David Sulzer, Ph.D., at the PDF Research Center at Columbia University Medical Center, studied the brains of mice with Parkinsonian symptoms, and used a variety of techniques to monitor communication in the brain. They already knew that in the brain, dopamine neurons and other brain cells “talk” to each other using chemical transmitters. They wanted to better understand one under-explored part of this brain circuitry in PD — one that uses the neurotransmitter called GABA (gamma-aminobutyric acid) to communicate. Results • As the mice lost dopamine in their brains, neurons involved in the brain’s GABA circuit lost the ability to hear themselves “talk.” • As neurons lost the ability to hear themselves talk, they became oversensitive to incoming messages. • Researchers tested how the oversensitive neurons reacted to dopamine-replacing drugs similar to levodopa. They found that the neurons overreacted to the medications by talking “too loudly” (that is, releasing too much GABA) which resulted in dyskinesia-like movements. • Researchers identified two chemical receptors — nei
ther of them based on dopamine — that may help the neurons “speak” normally again (and potentially ease dyskinesia). One is a GABA receptor; the other is known as cannabinoid receptor 1. What Does It Mean? This paper improves our understanding of brain circuitry in PD in general, shedding light on an underexplored brain circuit involving GABA. It also improves our understanding of dyskinesias, suggesting that they are caused not by levodopa alone, but by levodopa in combination with long-lasting brain changes that occur in PD. The discovery potentially opens a new door to treating a common PD symptom. The study results should also ease concerns that many people have about using Sinemet early in Parkinson’s. Why? Because they show that people with advanced PD are likely to develop dyskinesias quickly once they are exposed to Sinemet, whether or not they have used it earlier on. This finding suggests that there is no point in “saving Sinemet for later” in the early stages of PD, especially when it can effectively ease PD symptoms.