Dopamine is an important signaling molecule for nerve cells. Its concentration has so far been impossible to determine precisely with either high spatial or temporal separation. The new method made this possible: a research team from Bochum, Göttingen and Duisburg used modified carbon nanotubes that glow brighter in the presence of the messenger substance dopamine. These sensors visualize the release of dopamine from nerve cells with unprecedented resolution. This was reported in the journal by researchers led by Professor Sebastian Cruz from the Department of Physical Chemistry at Ruhr University Bochum (RUB) and Dr. James Daniel, as well as Professor Niels Brose from the Max Planck Institute for Multidisciplinary Sciences in Göttingen. PNAS from May 25, 2022.
Fluorescent changes in the presence of dopamine
The neurotransmitter dopamine, among other things, controls the reward center in the brain. If this signal transmission no longer works, it can lead to disorders such as Parkinson’s disease. Moreover, chemical signals are altered by drugs such as cocaine, and play a role in addiction-related disorders. “However, so far there has been no method that can simultaneously visualize dopamine signals with high spatial and temporal separation,” said Sebastian Cruz, head of functional interfaces and biosystems at RUB and a member of the Ruhr Explores Solvation Cluster of Excellence (RESOLV) and International. Higher School of Neurology (IGSN).
Here new sensors come into play. They are based on ultra-thin carbon tubes, about 10,000 times thinner than human hair. When irradiated with visible light, they glow in the near infrared range with wavelengths of 1000 nanometers and more. “This range of light is not visible to the human eye, but it can penetrate deeper into tissues and thus provide better and sharper images than visible light,” says Cruz. Also, there are far fewer background signals in this range that can skew the result.
“We have systematically modified this property by linking different short nucleic acid sequences to carbon nanotubes in such a way that they change their fluorescence when they come in contact with certain molecules,” explains Sebastian Cruz. This is how his research team was able to convert carbon nanotubes into tiny supernatants that specifically bind to dopamine and fluoresce more or less strongly depending on dopamine concentration. “We immediately realized that such sensors would be of interest to neurobiology,” says Cruz.
Covering healthy nerve cells with a sensory layer
To do this, the sensors must be moved in the immediate vicinity of the existing neural networks. Dr. Sofia Elizarova and James Daniel of the Max Planck Institute for Interdisciplinary Sciences in Göttingen have developed conditions for cell culture in which nerve cells remain healthy and can be covered with an extremely thin layer of sensors. This allowed researchers to first visualize individual dopamine release events along neuronal structures and gain insight into the mechanisms of dopamine release.
Cruz, Elizarova and Daniel are convinced that the new sensors have great potential: “They give a new idea of the plasticity and regulation of dopamine signals,” – says Sofia Eizarova. “In the long run, they can also contribute to progress in the treatment of diseases such as Parkinson’s disease.” In addition, additional sensors are currently being developed that can be used to make other signaling molecules visible, for example, to identify pathogens.
The study was conducted by researchers from Physical Chemistry II Ruhr University Bochum and the Max Planck Institute for Interdisciplinary Sciences in Göttingen, teams from the Institute of Physical Chemistry at the University of Göttingen, the Center for Integrative Physiology and Molecular Medicine at the University of Saarland and the Duron Institute.
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