Discovery could immediately suggest new avenues for drug development


Researchers at Oregon Health & Science University have found that the neurotransmitter adenosine effectively acts as a brake on dopamine, another well-known neurotransmitter involved in motor control.

Scientists have discovered that adenosine works in a sort of push-pull dynamic with dopamine in the brain; the finding published today in the journal Nature.

“There are two neural circuits: one that helps promote action and one that inhibits action,” said lead author Haining Zhong, Ph.D., a scientist at OHSU Vollum Institute. “Dopamine promotes the first circuit to allow movement, and adenosine is the ‘brake’ that promotes the second circuit and brings balance to the system.”

The finding could immediately suggest new avenues for drug development to treat the symptoms of Parkinson’s disease, a movement disorder where loss of dopamine-producing cells has been widely implicated as a cause.

Scientists have long suspected that dopamine is influenced by an opposing dynamic of neural signaling in the striatum – a critical brain region that mediates movement with reward, motivation, and learning. The striatum is also the main region of the brain affected in Parkinson’s disease by the loss of dopamine-producing cells.

“People have long suspected that there must be this push-pull system,” said co-author Tianyi Mao, Ph.D., a Vollum scientist who happens to be married to Zhong.

In the new study, researchers have for the first time clearly and definitively revealed that adenosine is the neurotransmitter that acts in an opposite direction to dopamine. The study, involving mice, used new genetically modified protein probes recently developed in the Zhong and Mao laboratories. An example of this technology was highlighted last month in a study published in the journal Natural methods.

Notably, adenosine is also well known as the receptor on which caffeine acts.

“Coffee acts in our brain through the same receptors,” Mao said. “Drinking coffee lifts the adenosine brake.”

In addition to Zhong and Mao, Lei Ma, Ph.D. of the Vollum Institute is the first author. Co-authors include Julian Day-Cooney, Ph.D., Michael A. Muniak, Ph.D., and Maozhen Qin du Vollum; and, Omar Jaidar Benavides, Ph.D., and Jun B. Ding, Ph.D., of Stanford University.

This work was supported by two BRAIN Initiative awards to Zhong and Mao through the National Institutes of Health, awards U01NS094247 and R01NS104944; as well as three awards through the NIH National Institute of Neurological Disorders and Stroke, award R01NS081071 to Mao and R21NS097856 and R01NS127013 to Zhong.

Source of the story:

Materials provided by Oregon Health and Science University. Original written by Erik Robinson. Note: Content may be edited for style and length.


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