New Tiny Sensors Detect Dopamine in High Resolution in Nerve Cells
Scientists have developed tiny sensors that allow the high-resolution detection of dopamine — the brain chemical messenger progressively lost in people with Parkinson’s disease — in nerve cells grown in the lab.
“These sensors visualise the release of dopamine from nerve cells with unprecedented resolution,” according to a press release from Ruhr-University Bochum, in Germany, which noted that the technology uses carbon tubes that glow brighter in the presence of dopamine.
The new detection method could help make progress in the treatment of Parkinson’s and other neurological disorders, the investigators say.
The findings were described in “A fluorescent nanosensor paint detects dopamine release at axonal varicosities with high spatiotemporal resolution,” a study published in the journal PNAS.
Dopamine is a neurotransmitter, a chemical messenger that allows nerve cells (neurons) to communicate and, among other functions, helps regulate movement. The loss of dopamine, due to the death of dopaminergic or dopamine-producing neurons in the brain, gives rise to Parkinson’s symptoms.
A better understanding of the release of dopamine by nerve cells is key to determining what goes awry in diseases like Parkinson’s. However, such understanding has been limited due to a lack of detection methods with sufficient resolution, both in time and space.
“Until now there was no method that could simultaneously visualize the dopamine signals with high spatial and temporal resolution,” said Sebastian Kruss, PhD, a professor at the Ruhr-University Bochum and the study’s co-lead author.
Now, a team led by Kruss and including researchers from the Ruhr-University Bochum and the Max Planck Institute for Multidisciplinary Sciences, in Göttingen, also in Germany, developed a near-infrared fluorescent dopamine nanosensor. It is designed to visualize dopamine release from nerve cells with unprecedented resolution.
The sensors are made of ultra-thin carbon tubes — 10,000 times thinner than a human hair. When irradiated with visible light, they glow in the near-infrared range in the presence of certain molecules.
“This range of light is not visible to the human eye, but it can penetrate deeper into tissue and thus provide better and sharper images than visible light,” Kruss said.
“We have systematically modified this property by binding various short nucleic acid sequences to the carbon nanotubes in such a way that they change their fluorescence when they come into contact with defined molecules,” he said. Of note, nucleic acids play a primary role in the storage of genomic information in cells, and come as DNA and RNA.
This means that the intensity of the fluorescence should increase in the presence of higher amounts of dopamine.
“We immediately realized that such sensors would be interesting for neurobiology,” Kruss added.
The researchers tested the new sensors — called AndromeDA — in lab tests. For this, Sofia Elizarova, PhD, and James Daniel, PhD, from Max Planck, developed a cell culture system in which dopaminergic neurons from mice were coated with an extremely thin layer of sensors.
Results showed that AndromeDA was successful at detecting with high spatial and temporal resolution the release of dopamine from axonal varicosities. These small, bead-like structures along nerve fibers are key in the communication between neighboring nerve cells.
The team further developed a machine learning-based tool to analyze dopamine release from up to 100 dopaminergic varicosities. The analysis revealed its heterogeneity, with only a fraction of varicosities — about 17% — actively releasing dopamine.
Moreover, dopamine release required the presence of Munc13-type proteins, “validating the utility of AndromeDA as a tool to study the molecular and cellular mechanism of [dopamine] secretion,” the team wrote.
Overall, the sensors “provide new insights into the plasticity and regulation of dopamine signals,” said Eizarova. “In the long term, they could also facilitate progress in the treatment of diseases such as Parkinson’s.”