Endocannibinoids to Rescue Parkinson’s Brains
A recent study from the lab of Robert Malenka, MD, PhD, Pritzker Professor of Psychiatry and Behavioral Sciences at Stanford University Medical School, has found naturally occurring endocannabinoids (substances similar to the active compounds in marijuana) in the brain that when stimulated, contributed to a dramatic improvement in mice with a condition like Parkinson’s.
Endocannabinoids, naturally synthesized marijuana like substances that occur in the brain were discovered in the late 1980s and research in the early 1990s found them to be essential bio-regulation. Research suggests they have a role in inflammation and endocrine activities and also serve as messengers for other neurological and immunological conditions. Cannabinoid receptors are located all over the brain, however their roles and functions are still being researched. It is not known why they are not always activated by naturally occurring endocannabinoids
Dr. Malenka and his post-doctoral researcher, Anatol Kreitzer, PhD, focused their attention on the striatum, because it is prominent to multiple neurological disorders, including PARKINSON’S DISEASE. Dopamine is the principle neurotransmitter in the striatum, which when depleted, causes the loss of movement and rigidity experienced by people with PARKINSON’S DISEASE. While studying the striatum, they became aware that there were many cell types that appeared alike under the microscope, but only became distinguishable when mice were specially bred to have specific cells stained with fluorescent dyes. With two cell types clearly identified, they were able to probe communication and activity between the cells. They identified a unique interaction between those two cells. One cell was involved with initiating movement and the other with restraining movement, and acting together to determine appropriate movement. Endocannabinoids are the “messengers” that use dopamine to cause the cells to interact. When dopamine is absent, the endocannabinoids begin to break down, causing the initiation of movement to halt and restraint of movement to become dominant.
Introducing more dopamine into the brains to the mice resulted in only a slight improvement in movement. Using a new drug to halt the enzymatic breakdown of the endocannabinoids did nothing. But introducing a combination of dopamine replacement and the enzyme that stopped the breakdown of the endocannabinoids resulted in the mice going from completely frozen to being able to move freely in only 15 seconds.
This study is exciting on many levels, from distinguishing the subtle differences in cell types in the striatum, to finding the communication loops between previously inconspicuous cells and mostly from finding a way to restore the balance to that interrupted cell circuitry to initiate the return of movement in the Parkinson-like mice. While it is immediate good news for the mice involved, it will still be quite a matter of more research and time before the implications of this study are fully researched and the results translated to good news for human studies. It does reveal a potential new therapeutic approach to finding better treatment for the symptoms of PARKINSON’S DISEASE.
Stanford School of Medicine News Release 2-27-14
Review by Marcia McCall