FEL sheds new light on Parkinson’s

DURHAM, NC-In a finding that may offer clues about Parkinson’s disease, a team led by Duke University researchers used the university’s free-electron laser (FEL) in conjunction with photoelectron emission microscopy (PEM) and atomic force microscopy (AFM) to image the structure of neuromelanin.

DURHAM, NC-In a finding that may offer clues about Parkinson’s disease, a team led by Duke University researchers used the university’s free-electron laser (FEL) in conjunction with photoelectron emission microscopy (PEM) and atomic force microscopy (AFM) to image the structure of neuromelanin.

Scientists previously determined via chemical analysis that neuromelanin comprises two pigments: eumelanin, found in black-haired people, and pheomelanin, found in redheads. But how those pigments are arranged structurally remained unknown, which could be of critical importance in better understanding disease.

Oxygen activation is suspected of playing a role in the neurogenic cascade of events behind Parkinson’s disease. In this latest study, the Duke researchers gained evidence that neuromelanins isolated from human brains have cores of oxygen-activating pheomelanin covered by a protective surface of eumelanin.

“This is the first piece of morphological data about how these pigments are constructed,” said study leader John Simon, professor of chemistry at Duke. Other researchers in the study, published in the Sept. 25 Proceedings of the National Academy of Science, were Glenn Edwards, director of the Duke University Free Electron Laser Laboratory; Robert Nemanich and Jacob Garguilo of North Carolina State; and Fabio Zucca and Alberto Albertini of the Italian Institute of Biomedical Technologies. “Of the two types of pigment in the brain, one is more anti-oxidant than the other and there are ideas that they are intermingled in either a random or structured way. We wanted to know what the oxidation potential looks like across the granules.”

According to the researchers, neuromelanin granules begin appearing in human brains between ages 3 and 5 and their concentrations increase steadily thereafter. However, neuromelanin levels drop precipitously in the brains of Parkinson’s patients, who also experience a death of brain cells that are darkly pigmented and an increase in brain tissue concentrations of the metal iron. The Duke FEL study was designed to determine how neuromelanin contributes to this degradation and to understand what the pigment is and how it changes over the course of a patient’s life.

“What you see in a Parkinson’s brain is about a third of the amount of pigment found in a normal brain,” Simon said. “So if it is metabolism and loss of pigment that contributes to disease, whatever causes the degradation produces material that contributes to the oxidation. The question is what is cause and what is effect. We can autopsy the brain after death and see what the degradation is, but we don’t have a picture of how the brain is deteriorating during the disease and prior to death.”

Simon and his colleagues used a PEM coupled to the tunable OK-4 FEL to obtain wavelength-dependent ultraviolet images (248-418 nm) of isolated neuromelanin samples deposited on a silicon substrate. Simon says that while it may not be the most practical in terms of size and mobility, the FEL is actually the best laser to use for studies like these because of its extreme tunability and beam characterization. He and his colleagues are currently doing some additional experiments with a frequency-doubled argon-ion laser, but he says that the ionization potential of human pigments requires an easily tunable laser because different pigments have different potentials.

“Could you take a conventional UV laser and do this? Yes. Could you do it in half an hour? No,” Simon said. “With the FEL, in 30 minutes it is easy to go from 220 to 400 nm, and all the parameters hold constant, the energy is known, the beam is well-characterized, and the spot stays in the same place. The FEL is the perfect choice for this application and an ideal source for tuning through the entire UV range.”

-Kathy Kincade

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