By Michelle Koidin Jaffee
Researchers have developed a novel method to rapidly identify specific immune cells in human and mouse blood samples, a discovery that could provide a new tool to aid in detecting and monitoring a range of disorders, including drug addiction, attention deficit hyperactivity disorder (ADHD) and Parkinson’s disease. The discovery, by a team from the National Institute on Drug Abuse and UF’s McKnight Brain Institute, was reported Jan. 24 in JACS Au, an open access journal of the American Chemical Society.
Researchers used human and mouse blood samples to reveal that a specially designed fluorescent compound can effectively highlight immune cells that express the dopamine transporter (DAT), which serves to bring dopamine back into neurons for reuse. These immune cells are associated with a range of neurological disorders, and the discovery opens new avenues for understanding and potentially treating these complex conditions, said UF neuroscientist Habibeh Khoshbouei, Pharm.D., Ph.D., a co-author of the study.
The new paper is the latest advance by Khoshbouei’s lab in pursuit of a user-friendly and accessible tool to detect DAT-expressing immune cells in blood circulation. Previous research by her lab has shown that DAT-expressing peripheral immune cells are altered in an array of neurological disorders.
Now, with senior author Amy Hauck Newman, Ph.D., scientific director of the National Institute on Drug Abuse – Intramural Research Program, and first author Gisela Andrea Camacho-Hernandez, Ph.D., a postdoctoral fellow in Newman’s lab, the research team has developed a novel fluorescent compound called GC04-38, which they showed binds to DAT. An accompanying illustration designed by Camacho-Hernandez is featured as the supplemental cover of JACS Au.
“While the Khoshbouei lab has previously demonstrated that measuring DAT expression in circulating immune cells can detect Parkinson’s disease and monitor its progression in patients, the procedures are multistep,” said Adithya Gopinath, Ph.D., a postdoctoral fellow in the MBI’s Gator NeuroScholars program and co-author of the paper. “In the current research, we show a one-step method allowing a rapid and reliable detection of DAT-expressing cells.”
Previous research by the Khoshbouei lab has shown a link between increased DAT expression in peripheral immune cells and dopamine neuronal loss in Parkinson’s, though to date the mechanism underlying this connection is unclear. DAT serves as a drug target for ADHD medications, while addictive drugs such as cocaine and methamphetamine are DAT inhibitors that block the removal of dopamine from the synapse, allowing it to accumulate.
For the current study, the research team used flow cytometry and the novel GC04-38 compound to analyze human and mouse blood immune cells and detect DAT-expressing ones.
This illuminates fundamental understanding of DAT expression and activity in peripheral blood mononuclear cells — both in health and disease, the researchers reported.
“This discovery expands the scope of studying DAT-expressing immune cells, potentially bringing this tool to the hands of many more researchers investigating brain-to-immune system communication,” Gopinath said.