Parkinson's disease: Boosting dopamine promotes movement

New research with implications for the treatment of Parkinson's disease suggests that when we want to move, all our brain needs is a quick burst of dopamine.

The results, by scientists at the Champalimaud Center for the Unknown in Portugal as well as Columbia University in New York City, NY, question the idea that the brain needs a constant level of dopamine for normal movement.

A report on the study, published in the journal Nature, describes how immediately before they initiated movements, the associated neurons, or nerve cells, showed peaks in dopamine activity.

"Our most important result," says first study author Dr. Joaquim Alves da Silva, a psychiatrist and neuroscientist from the Champalimaud Center and the Nova University of Lisbon in Portugal, "is that we showed, for the first time, that the change in neural activity is necessary to promote movement."

"And, also for the first time," he continues, "we showed that the dopamine peak that precedes movement initiation does not only regulate initiation, but also regulates movement vigor."

Death of dopamine cells leads to Parkinson's

Parkinson's disease is a progressive disorder that develops when dopamine-producing cells in the substantia nigra, which is an area of the brain that controls movement, die.

Dopamine is a neurotransmitter, or a chemical messenger that carries signals between neurons. It is linked to a number of brain functions, including the control of movement and behavior that is associated with reward and pleasure.

The main symptoms of Parkinson's disease include tremor, stiffness, slowness of movement, and impaired coordination and balance. As the symptoms progress, they make it harder to talk, walk, carry out everyday tasks, and live independently.

Although the disease mostly affects people over the age of 60, around 4 percent of Parkinson's cases are diagnosed in those under the age of 50.

Worldwide, there are more than 10 million individuals living with Parkinson's disease. In the United States — where approximately 60,000 people are diagnosed with Parkinson's every year — the total cost of the disease is estimated to be $25 billion per year.

There is currently no cure for Parkinson's disease. However, there are drugs that can substantially relieve symptoms for many people by helping to replenish and maintain the brain's diminishing supply of dopamine.

Difficulty is movement initiation, slowness

The new study is particularly significant because it suggests that there might be a better way to correct dopamine shortage.

Dr. Alves da Silva explains that individuals with Parkinson's "do not have a global motor problem," but a specific one. Under the right circumstances, they can perform complex motor tasks. For example, if given a push at the right time, they can even ride a bicycle.

"The patients' problem," he adds, "is in the difficulty to initiate movement and in the slowness of movement." It was this observation that spurred the team to investigate further.

For the new study, the researchers used a technique called optogenetics, which employs laser light to rapidly stimulate neuron activity in the brains of mice.

Optogenetics is a relatively new technology that is changing "the landscape of neuroscience" by improving our understanding of how particular brain circuits work in health and disease.

Dr. Alves da Silva says that they used it to ensure that they only recorded activity in the dopamine-producing neurons of the mice's substantia nigras.

Burst of dopamine neuron activity

The scientists recorded what happened in the mice's brains as they moved freely in an open space. Using motion sensors, they could detect when the animals started moving and pinpoint the activity of the dopamine-producing cells in the period leading up to their moves.

The results showed that the activity of the dopamine-producing neurons peaked just before the mice started a given movement.

Then, in another experiment, they allowed the mice to roam freely, except that they manipulated the activity of their dopamine-producing neurons by using the laser to switch them on and off.

Again, with the help of the motion sensors, they could link this to when the mice were moving and not moving.

Dr. Alves da Silva notes that activating the dopamine-producing neurons when the mice were not moving "for half a second was enough to promote movement — and with more vigor — than without these neurons' activity."

But, if they activated the neurons when the mice were already in motion, the animals continued as they were — there was not change in the movement or its vigor, which they defined from changes in acceleration.

Results may also explain link to motivation

The researchers found same result when they switched off the dopamine-producing neurons in the middle of an ongoing movement — there was no change in the movement or its vigor.

"These results," explains senior author Rui Costa, a professor of neuroscience and neurology who works at Columbia University, "show that the activity of dopamine neurons can act as a gate to permit or not the initiation of movements."

"They explain why dopamine is so important in motivation, and also why lack of dopamine in Parkinson's disease leads to the symptoms that it does," he adds.

One of the drugs that is currently used to treat Parkinson's disease is levodopa, which raises the body's level of dopamine.

"But levodopa elevates dopamine all the time, not just when we want to move," says Prof. Costa, adding that long-term use of the drug also leads to dyskinesia, a condition characterized by involuntary and erratic movements.

"Our study suggests that strategies that would boost dopamine when there is a desire to move would work better."

Prof. Rui Costa