Researchers at the University of Michigan Life Sciences Institute have created a tool that aids in discovering how neuronal signals are utilized by neurons, which they announced in an article published April 22. The new tool called a SPOTIT, or a Single-chain Protein-based Opioid Transmission Indicator Tool, probes inside the brain to check for specific neurotransmitters. The project was based on the collaboration of the Peng Li Lab and the Wenjing Wang Lab, which both focus on neuronal interactions within the brain.
In an interview with The Michigan Daily, Peng Li, the principal investigator of the Peng Li Lab and an author of the study, said the combination of the two labs’ specialties was the reason for his enthusiasm for the collaboration.
“One particular part that is really exciting is the collaboration between two different labs with different expertise,” Li said. “So (Wang’s) lab is developing these tools and we are helping them apply that into the brain.”
The study focused on how chemicals get processed through G protein-coupled receptors, proteins that sit on the surface of cells, recognize outside substances and transmit signals back through the cell membrane. GPCRs play a key role in biological functions such as sleeping, breathing and eating.
The chemicals that the labs observed being processed through GPCRs included dopamine, also known as the “feel good” neurotransmitter, and serotonin, another neurotransmitter that plays key roles in mood and sleep. With the SPOTIT sensor, scientists will be able to better understand many processes occurring within the human brain in connection to these chemicals, such as the origins of addiction and emotion regulation.
In an interview with The Daily, Wenjing Wang, principal investigator of the Wenjing Wang Lab and another author of the article, said the study focused on the action of opioid signaling, which is the process of how neurotransmitters bind to opioid receptors on a cell membrane.
“There are a lot of drugs targeting these neuromodulatory systems,” Wang said. “So in our lab what we are interested in (is) opioid signaling, and how places that impair modulation (can) also cause addiction. … We are also very interested in just knowing where these endogenous opioid peptides are released and how they regulate emotions.”
Specific drugs administered to patients can reach their desired treatment destinations in the body in different amounts, known as bioavailability. Wang said these drugs can cause specific and different interactions, which the SPOTIT tool can help reveal.
“The other question is how synthetic opioids are,” Wang said. “There are different types of synthetic opioids, such as morphine, fentanyl … they are very frequently used as care medications but excite differently in patients, so we also want to see their bioavailability in the brain.”
The experiment used a mouse model to test the SPOTIT sensor. Li said opioids were introduced to the subjects to test if the sensor could see the drugs’ presence in the brain.
“We could apply these sensors into the mouse’s brain and treat the animal with a synthetic opiate,” Li said. “And then we wanted to see the opiated-treated animal, and (we found) in this particular case, especially in the breathing-control regions in the brainstem, there is an elevated sense of activity. We did see that the drug really goes into the brainstem and is active there, which shows that (the drug) is working in-vivo in the mouse brain.”
One drawback to using the SPOTIT tool is the time consumption of the image development, which can take multiple hours until it is fully completed. In an interview with The Daily, Chemistry Ph.D. candidate Aubrey Putansu, a member of the Wenjing Wang Lab, said the additional time between the drug injection and viewing the final SPOTIT image interfered with the efficiency of the process.
To solve this issue, Putansu has started an additional project that will prioritize targeting the fluorescent protein for more efficient resolution. The labs will also continue to work on expanding the applications of the SPOTIT tool, hoping to generalize the sensor to allow it to detect things other than just the opioids in the brain.
“Currently the major limitation of our tool is the slowness, we’d call it a temporal resolution,” Putansu said. “So this idea that you could correlate your signal to the exact time that either a behavior happened or that you administered some sort of drug and having to wait, and especially having to wait not just a little bit, but hours … that’s really significant.”
Daily Staff Reporter Chiara Dettin can be reached at chiarald@umich.edu.
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