Live neuron probe

01 September 2015 | Research
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Cultured rat neurons stained with NeuO

A fluorescent dye that reveals living nerve cells can now enable researchers to gain insights into neurological disorders in the body, such as Alzheimer's and Parkinson's disease.

A group of scientists from NUS and the Agency for Science, Technology and Research (A*STAR) has designed the world's first such probe that can explicitly label and image live neurons in the brain. This discovery can potentially be incorporated in diagnostic tools, surgical aids and drug delivery.

Neuron Orange (NeuO), an organic dye created by the team, allows real-time imaging of neurons both in the petri dish and within the organism. Before this, there was no existing chemical that could stain live neurons selectively, while antibodies are employed for only dead nerve cells.

The activity of neurons dictates human thought and movement but little is known about the mechanisms controlling their form and function owing to the dearth of tools to visualise these nerve cells in the natural state.  

The Singapore breakthrough, published in Angewandte Chemie International Edition early this year, addresses current limitations in live neuron imaging. Besides its possible use in neuronal targeting applications, it can also help prospective studies in neuron development, networking and degeneration.

Although fluorescent proteins are able to visualise neurons, their complicated and laborious preparation deters general use. NeuO, however, can be easily introduced intravenously instead of having to genetically engineer an organism to express the protein.

Led by Professor Chang Young-Tae from the Department of Chemistry, the team developed NeuO over four years and tested it on zebrafish and mice. The non-toxic chemical crosses the blood-brain barrier and selectively stains neurons fluorescent orange immediately. The fluorescence passes out of the body harmlessly in a few hours.

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Prof Chang (centre) with PhD student Er Jun Cheng (left) and SBIC Research Fellow Dr Teoh Chai Lean develop the probe for live neurons. Another major investigator of the team was recently graduated student Cheryl Leong (not in picture)

Prof Chang, who also heads the Laboratory of Bioimaging Probe Development in A*STAR's Singapore Bioimaging Consortium (SBIC), said his group adopted an innovative Diversity-Oriented approach, which is different from other probes that focus on specific targets. By screening large numbers of compounds on various cells, the team has established a huge library of more than 10,000 compounds. This toolbox enables rapid screening for subsequent tests on any type of cell.

Patents have been filed for both the approach and NeuO, and licensing is ongoing, Prof Chang revealed. The compound is being shared with other research groups around the world for neurological investigation.

The Singapore scientists are exploring ways to incorporate NeuO into multifunctional probes and also to make it emit at different colours to achieve simultaneous detections. Future clinical works will involve introducing NeuO into the body, said Prof Chang.