Scientists Identify Key Molecule

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Parkinson's Disease Concept The Missing Piece

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 the 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.

The researchers found that adenosine, a neurotransmitter, acts as a brake on another neurotransmitter, dopamine, which is involved in motor control. Oregon Health & Science University. The results were published in the journal naturereveals that adenosine and dopamine act in push-pull dynamics in the brain.

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

The discovery has the potential to immediately offer 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 the loss of dopamine-producing cells in the brain.

Haining Zhong and Tianyi Mao

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

Scientists have long suspected that dopamine affects the reverse dynamics 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 main brain region affected by the loss of dopamine-producing cells in Parkinson’s disease.

“Sceptics have suspected for a long time that this push-pull system exists,” said co-author Tianyi Mao, Ph.D., a scientist at Vollum who is married to Zhong.

In the new study, researchers have for the first time clearly and definitively identified adenosine as a neurotransmitter that acts in the opposite direction to dopamine. The mouse study used new genetically engineered protein probes recently developed in Zhong and Mao’s labs. An example of this technology was highlighted in a study published last month in the journal Nature Methods.

Note that adenosine is also known as the receptor affected by caffeine.

“Coffee works through the same receptors in our brain,” Mao said. “Drinking coffee lifts the brake applied 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 population and subcellular imaging of cAMP” by Crystian I. Massengill, Landon Bayless-Edwards, Cesar C. Ceballos, Elizabeth R. Cebul, James Cahill, Arpita Bharadwaj, Evan Wilson, Maozhen R., Matthew ” Whorton, Isabelle Baconguis, Bing Ye, Tianyi Mao, and Haining Zhong, 27 Oct 2022, Nature’s methods.
DOI: 10.1038/s41592-022-01646-5

The research was funded by two BRAIN Initiative awards to Zhong and Mao through the National Institutes of Health, as well as three awards to Zhong from the NIH National Institute of Neurological Disorders and Stroke.

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