Scientists have identified a key molecule

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Missing piece of the concept of Parkinson's disease

Parkinson’s disease is a progressive neurological disorder that affects movement and can cause tremors, stiffness, and difficulty with balance and coordination. It is caused by a loss of cells that produce dopamine, a neurotransmitter that plays a key role in the body’s movement and reward systems.

The discovery could immediately lead to new opportunities for drug development.

researchers of the Oregon Health and Science University. The findings, which were published in the journal Naturereveal that adenosine and dopamine operate in a back-and-forth dynamic in the brain.

“There are two neural circuits: one that helps promote action and the other that inhibits action,” said lead author Haining Zhong, Ph.D., a scientist at the 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 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 thought to be caused by a loss of dopamine-producing cells in the brain.

Haining Zhong and Tianyi Mao

Tianyi Mao, Ph.D., left, and Haining Zhong, Ph.D., scientists at the Vollum Institute at Oregon Health and Science University, led a new study that found that adenosine effectively acts as a brake on dopamine in the brain. Credit: Oregon Health and Science University

Scientists have long suspected that dopamine is influenced by an opposite dynamic of neural signaling in the striatum, a critical region of the brain that mediates movement along 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.

“For a long time, people suspected that there had to 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, the researchers revealed for the first time clearly and definitively that adenosine is the neurotransmitter that acts in the opposite direction to dopamine. The study, which involved mice, used new genetically modified protein probes recently developed in the labs of Zhong and Mao. An example of that technology was highlighted last month in a study published in the journal Nature Methods.

In particular, adenosine is also well known as the receptor that caffeine acts on.

“Coffee acts on 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, November 9, 2022, Nature.
DOI: 10.1038/s41586-022-05407-4

“Sensitive Genetically Encoded Sensors for In Vivo Subcellular and Population Imaging of cAMP” 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, October 27, 2022, Nature’s Methods.
DOI: 10.1038/s41592-022-01646-5

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 NIH National Institute of Neurological Disorders and Stroke, to Zhong.

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