"Fluorescent sensor paint" lights up key markers of Parkinson's disease
Addressing the shortage of dopamine that characterizes Parkinson's disease is a key objective of treatments old and new, but monitoring levels of the neurotransmitter that result from these interventions can be a tricky undertaking. Scientists have developed a promising new tool for this task described as a "fluorescent nanosensor paint," which glows brightly in the presence of dopamine to reveal its concentrations and spread in the brain.
The decline in dopamine production seen in Parkinson's is linked to the onset of motor symptoms such as tremors and poor balance, and while there is no complete cure for the condition, treatments can slow this process and improve a patient's quality of life. This includes the drug levodopa, which helps the brain produce more dopamine, and deep brain stimulation, which has been used for decades as a way of improving physical symptoms.
An accurate way of measuring dopamine would provide physicians with a powerful new way of monitoring the effectiveness of these treatments, and let them refine their approaches for improved patient outcomes. This is possible using electrodes to measure chemical activity in the brain, and in 2017 an MIT team produced a new array for long-term monitoring of dopamine across brain regions in real time. Other electrode systems have continued to improve the accuracy of this technique in the years since.
A research team led by scientists at Germany's Ruhr University Bochum has been pursuing an alternative approach, looking to offer new spatial and temporal resolution for dopamine readings. The technique begins with ultra-thin carbon nanotubes around 10,000 times thinner than a human hair. The scientists made some alterations that equipped these tiny tubes with new capabilities, enabling them to bind to dopamine and glow more or less brightly depending on its concentration.
“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,” explains study author Sebastian Kruss. “We immediately realized that such sensors would be interesting for neurobiology.”
The scientists then sought to test the sensors' potential in a functioning neuronal network, which they developed cell culture conditions for in the lab. Coating nerve cells with a very fine layer of their "fluorescent dopamine nanosensor paint" enabled the researchers to detect secretion of the neurotransmitter with a high spatial and temporal resolution they say wasn't possible previously. A purpose-built machine-learning algorithm also enabled the sensors to reveal dopamine release hotspots along neuronal structures for the first time.
“They provide new insights into the plasticity and regulation of dopamine signals,” says study author Sofia Eizarova. “In the long term, they could also facilitate progress in the treatment of diseases such as Parkinson’s.”
The results of these early investigations indicate that the novel sensors can serve as a tool to study the molecular and cellular machinery behind dopamine secretion. The scientists imagine adapting the technology for other uses too, possibly tuning it to light up signaling molecules that reveal pathogens, for example.
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: Ruhr University Bochum