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UB chemist discusses breakthroughs that could help treat Parkinson’s

If you think your workspace is cramped, consider Frank Bright’s for a moment.

Bright is a SUNY Distinguished Professor and the Henry M. Woodburn Chair in the Department of Chemistry in UB’s College of Arts and Sciences. He works mostly in an area that’s 50 nanometers wide.

One nanometer is a million times smaller than a millimeter, so Bright spends a lot of time in an area that provides room for, well, practically nothing.

Except, perhaps, the type of sensor that Bright and his colleagues are building.

Based on nanocrystals, these sensors are providing groundbreaking insights into neurotransmitter production and how their concentrations are measured in the brain.

Many researchers are trying to better understand neurotransmitter production using tools ranging from functional MRI (magnetic resonance imaging) to microelectrodes. These techniques have important applications, but they are imprecise, focusing on a brain region not a specific area/defect.

Bright says these existing tools can determine that an area of the brain is depleted of a neurotransmitter — dopamine for instance, which can cause Parkinson’s disease — but the methods are too coarse-grained to pinpoint an actual location.

“Imagine the water system for an entire city,” says Bright. “A coarse-grained image might be able to identify a leak, but to be effective, the system has to determine the location of the leak if the problem is going to be addressed.”

Neurotransmitters are molecules that carry information in the brain. They’re released by synapses that receive an electrical signal. Like a castaway releasing a message in a bottle with instructions for potential rescuers, neurotransmitters are released in the brain with instructions for cells and neurons to carry out specific duties.

“The issue with Parkinson’s, which is what we’re mostly interested in, is that it involves a down regulation of dopamine,” says Bright. “The brain has signaled a release, but a synapse doesn’t release enough dopamine.”

Functional MRIs, while powerful, provide only an approximate location of the misfiring synapses. A microelectrode provides more spatial refinement compared to MRI but, in comparison to an individual synapse, it is still 1,000-times too large.

But Bright’s sensors are typically 10 nanometers. That’s 10,000 times less than the thickness of a sheet of notebook paper and five times smaller than a synaptic junction.

By modifying the nanosensor’s surface chemistry, researchers can create small photoluminescent sensors that change how they emit light in the presence of specific neurotransmitters.

“In the case of dopamine, we modify the surface chemistry by attaching a small piece of DNA or RNA so that dopamine is recognized and bond to the surface of the nanocrystal,” says Bright. “The binding changes the crystal’s surface, which then changes the color of the emitted light.”

The nanocrystal also is treated with a targeting molecule that’s attracted to unique proteins on a synapse. This gets the sensor to the right spot to make its measurement before disappearing.

“The crystal’s existence is fleeting in fluid,” says Bright. “They dissolve in about 50 minutes to form silicic acid, which is intrinsic to the body.”

And it’s just the beginning.

In addition to measuring and targeting, Bright says someday these nanocrystals might even carry a payload that could be released in dopamine-deficient or other depleted synapses.

“That’s something we want to work on next.”

Again, finding the specific location is imperative. Randomly releasing neurotransmitters would overwhelm those areas of the brain that were functioning normally.

“It’s not like an insulin pump that indiscriminately releases insulin in the body that is distributed by the circulatory system,” says Bright. “The delivery of a neurotransmitter has to be focused on individual synapse level.”

Bright will discuss his research in the next Scholars on the Road lecture, “Lighting the Brain’s Neurotransmission Highway,” taking place tomorrow in Miami.

Now in its third season, Scholars on the Road features UB faculty members discussing their research and areas of expertise with alumni, taking the classroom experience and sharing it with UB alumni here in Buffalo and around the country.

By Bert Gambini