Challenging Parkinson’s Dogma: Dopamine may not be the only key player in this tragic neurodegenerative disease

Scientists may have discovered why the standard treatment for Parkinson’s disease is often effective for only a limited period of time. Their research could lead to a better understanding of many brain disorders, from drug addiction to depression, that share certain signaling molecules involved in modulating brain activity.

A team led by Bernardo Sabatini, Takeda Professor of Neurobiology at Harvard Medical School, used mouse models to study dopamine neurons in the striatum, a region of the brain involved in both movement and learning. In people, these neurons release dopamine, a neurotransmitter that allows us to walk, speak and even type on a keyboard. When those cells die, as they do in Parkinson’s patients, so does the ability to easily initiate movement. Current Parkinson’s drugs are precursors of dopamine that are then converted into dopamine by cells in the brain.

The flip side of dopamine dearth is dopamine hyperactivity. Heroin, cocaine and amphetamines rev up or mimic dopamine neurons, ultimately reinforcing the learned reward of drug-taking. Other conditions such as obsessive-compulsive disorder, Tourette syndrome and even schizophrenia may also be related to the misregulation of dopamine.

In the October 11 issue of Nature, Sabatini and co-authors Nicolas Tritsch and Jun Ding reported that midbrain dopamine neurons release not only dopamine but also another neurotransmitter called GABA, which lowers neuronal activity. The previously unsuspected presence of GABA could explain why restoring only dopamine could cause initial improvements in Parkinson’s patients to eventually wane. And if GABA is made by the same cells that produce other neurotransmitters, such as depression-linked serotonin, similar single-focus treatments could be less successful for the same reason.

“If what we found in the mouse applies to the human, then dopamine’s only half the story,” said Sabatini.