The OHSU discovery could reveal new ways to treat symptoms of Parkinson's disease

The OHSU discovery could reveal new ways to treat symptoms of Parkinson's disease

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

Scientists found that adenosine works in a kind of push-pull dynamic with dopamine in the brain; the discovery published today in the journal Nature.

There are two neural circuits: one that promotes action and one that inhibits action. Dopamine promotes the first circuit to allow movement, and adenosine is the ‘brake’ that promotes the second circuit and brings the system into balance.”

Haining Zhong, Ph.D., senior author, scientist, OHSU Vollum Institute

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The discovery could immediately open new avenues for drug development to treat symptoms of Parkinson's disease, a movement disorder in which the loss of dopamine-producing cells is widely thought to be the cause.

Scientists have long suspected that dopamine is influenced by an opposite 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 by loss of dopamine-producing cells in Parkinson's disease.

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

In the new study, researchers have for the first time clearly and unambiguously identified adenosine as the neurotransmitter that works in contrast to dopamine. The study, which involved mice, used novel genetically engineered protein probes recently developed in the laboratories of Zhong and Mao. An example of this technology was highlighted last month in a study published in the journal Nature Methods.

Adenosine is particularly known as the receptor on which caffeine acts.

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

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

Source:

Oregon Health & Science University

Reference:

Ma, L., et al. (2022) Locomotion activates PKA through dopamine and adenosine in striatal neurons. Nature. doi.org/10.1038/s41586-022-05407-4.

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