Findings From Nerve-Cell Probe Could Point Way to New Treatments

Techniques for visualizing bulk quantities of nerve receptors abound. But now a probe has been developed that allows one to visualize single nerve receptors.

The probe was developed by Tania Vu, Ph.D., an assistant professor of biomedical engineering at Oregon Health and Science University, along with Paul Greengard, Ph.D., Marc Flajolet, Ph.D., and Katye Fichter, Ph.D., of Rockefeller University. (Greengard shared the 2000 Nobel Prize for Physiology or Medicine with Arvid Carlsson, M.D., Ph.D., and psychiatrist Eric Kandel, M.D.).

They reported their achievement in the October 12, 2010, online edition of the Proceedings of the National Academy of Sciences.

Their probe consists of small, intensely fluorescent nanocrystals called “quantum dots.” They have used it to track individual serotonin receptors as the receptors moved through the neuronal cell membrane and back again. They now plan to use the probe to learn more about how serotonin receptors interact with a protein called p11. They know that the p11 protein increases the number of serotonin receptors on the nerve cell membrane. But how does that protein do this? Does it attach the receptors to something that slows their movement into the cell, or does it increase the recycling of the receptors back to the surface?

Answering such questions, Vu told Psychiatric News, “could bring us closer to the molecular mechanisms of depression or other psychiatric illnesses.” In other words, their probe could be used to explore the molecular mechanisms of any illness involving nerve receptor dysfunction, including schizophrenia and affective disorders.

Their probe could also lead to the development of better drugs for patients with psychiatric disorders, they believe. “Many drugs have been developed to target nerve receptors that play a role in psychiatric illnesses, but the physiological response of the receptors to these drugs is very difficult to determine,” Vu explained. “Using quantum dot-tagged nerve receptors, an array of different drugs could be assayed to determine their effect on the internalization and recycling rates of those receptors. Those drugs that produced the desired physiological response could then be further developed, hopefully leading to the emergence of more effective drugs for patients.”

As for how their probe might benefit psychiatry during the next several years, Vu explained, “With more work, we hope to be able to develop an in vivo assay system that will allow us to monitor the trafficking behavior of receptors in response to drugs.”

The research was funded by the U.S. Army Medical Research and Material Command's Telemedicine and Advanced Technology Research Center.

An abstract of “Kinetics of G-Protein-Coupled Receptor Endosomal Trafficking Pathways Revealed by Single Quantum Dots” is posted at <www.pnas.org/content/107/43/18658.abstract>.