WEDNESDAY, Feb. 7, 2007 (HealthDay News) -- Manipulation of brain molecules similar to those found in marijuana provided dramatic relief of Parkinson's-like symptoms in mice, researchers report.
"This might be a target for treatment that could cure the motor deficits seen in Parkinson's disease," said lead researcher Anatol Kreitzer, whose team published the findings in the Feb. 8 issue of Nature.
Kreitzer emphasized two points, however -- that a lot of work must be done before human trials can begin, and that the study results do not support smoking marijuana as a way to help Parkinson's patients.
The study did involve cannabinoids, molecules that are similar to those found in marijuana. But these cannabinoids occur naturally in the brain, and the study hinged on targeting specific cannabinoids.
"When you smoke a joint, you activate cannabinoid receptors all over the brain," explained Kreitzer, who now is a postdoctoral fellow at Stanford University and will soon move to a research position at the University of California, San Francisco. "That is indiscriminate," Kreitzer said. "In general, you need more specific signaling. Our approach involved only regions of the brain or cells that release dopamine."
Dopamine is crucial, because a lack of that chemical produces the movement problems seen in Parkinson's disease. Kreitzer and Dr. Robert Malenka, professor in psychiatry and behavioral sciences at Stanford, focused on dopamine in the striatum, a region of the brain implicated in Parkinson's disease and a number of other disorders.
"This particular part of the brain doesn't have any obvious anatomy," Kreitzer said. "If you just look at the cells, they all look alike. But it turns out that there are two specific circuits there involved in the control of movement -- a direct pathway that activates motion and an indirect pathway that inhibits motion."
The researchers worked with mice engineered to have a fluorescent protein in one of those circuits. They found that dopamine acts differently in the two circuits. When dopamine is depleted in the pathway that inhibits movement, it becomes overly active.
"The mice that didn't have dopamine in that circuit are completely frozen," Kreitzer said. "They don't walk around at all. To restore plasticity, we tried to activate the dopamine signal."
The mice were given both dopamine and a drug being developed for treatment of anxiety, which acts by slowing the breakdown of brain cannabinoids. "The animals started walking around immediately," Kreitzer said. "There was a five- or sixfold increase in motor activity. If you inhibit the breakdown of these endocannabinoids, you enhance activity even in mice that lack dopamine."
Research now will go in a number of directions, Kreitzer said. "We'd like to understand some other functions of these compounds," he said. Several stages of animal work must be done before human trials can be considered, Kreitzer added.
"A potential role for endocannabinoids for Parkinson disease represents an exciting new area for Parkinson research," said Dr. Michael S. Okun, medical director of the National Parkinson Foundation, which helped fund the research.
Although more study is needed, the work "sheds some light on potentially relevant targets and strategies for treatment of this neurodegenerative disease," said Okun, who is also co-director of the Movement Disorders Center at the University of Florida, Gainesville.
More information
There's more on Parkinson's disease at the National Parkinson Foundation.
