The discovery could immediately lead to new opportunities for drug development.
Adenosine, a neurotransmitter, has been found to act as a brake on dopamine, another neurotransmitter involved in motor control, by researchers at Oregon Health & Science University. The findings, which were published in the journal Nature, reveal that adenosine and dopamine operate in a push-pull dynamic in the brain.
“There are two neuronal circuits: one that helps promote action and the other that inhibits action,” said senior author Haining Zhong, Ph.D., a scientist with the OHSU Vollum Institute. “Dopamine promotes the first circuit to enable movement, and adenosine is the ‘brake’ that promotes the second circuit and brings balance to the system.”
The discovery has the potential to immediately suggest new avenues for drug development to treat the symptoms of Parkinson’s disease. Parkinson’s disease is a movement disorder that is believed to be caused by the loss of dopamine-producing cells in the brain.
Scientists have long suspected that dopamine is influenced by an opposing dynamic of neuronal signaling in the striatum — a critical region of the brain that mediates movement along with reward, motivation, and learning. The striatum is also the primary brain region affected in Parkinson’s disease by the loss of dopamine-producing cells.
“People for a long time suspected there has to be this push-pull system,” said co-author Tianyi Mao, Ph.D., a scientist at the Vollum who happens to be married to Zhong.
In the new study, researchers for the first time clearly and definitively revealed adenosine as the neurotransmitter that acts in an oppositional sense with dopamine. The study, involving mice, used novel genetically engineered protein probes recently developed in the Zhong and Mao labs. An example of that technology was highlighted last month in a study published in the journal Nature Methods.
Notably, adenosine is also well known as the receptor that caffeine acts upon.
“Coffee acts in our brain through the same receptors,” Mao said. “Drinking coffee lifts the brake imposed by adenosine.”
References: “Locomotion activates PKA through dopamine and adenosine in striatal neurons” by Lei Ma, Julian Day-Cooney, Omar Jáidar Benavides, Michael A. Muniak, Maozhen Qin, Jun B. Ding, Tianyi Mao and Haining Zhong, 9 November 2022, Nature.
“Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo” by Crystian I. Massengill, Landon Bayless-Edwards, Cesar C. Ceballos, Elizabeth R. Cebul, James Cahill, Arpita Bharadwaj, Evan Wilson, Maozhen Qin, Matthew R. Whorton, Isabelle Baconguis, Bing Ye, Tianyi Mao and Haining Zhong, 27 October 2022, Nature Methods.
The study was funded by two BRAIN Initiative awards to Zhong and Mao through the National Institutes of Health, as well as three awards through the National Institute of Neurological Disorders and Stroke of the NIH, to Zhong.