Detecting Metals in the Brain with Laser Ablation-ICP-MS

Spectroscopy recently spoke with Dr. Dominic Hare, a senior research officer at the Florey Institute of Neuroscience and Mental Health in Australia, about his work using laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP-MS) to study metals in the brain. His research highlights the role that iron plays in Parkinson’s disease in the hopes to better understand the causes of the disease and eventually find an appropriate treatment.

At ASMS this year you presented research highlighting the role that high iron and high dopamine play in Parkinson’s disease, specifically the chronic degeneration of neurons in the substantia nigra pas compacta region of the brain. How did you get involved in this research?

I was studying forensic chemistry during my undergraduate years, and during this period I worked in a forensic pathology laboratory, where I became fascinated with the brain. When I started PhD studies in analytical chemistry, I wanted to find ways to integrate cutting edge technology into meaningful areas of health research. Being a relatively small yet productive scientific community, Australia is a fantastic place to build new collaborations, and I’ve been working with The Florey Institute of Neuroscience and Mental Health for around five years to help find new ways to apply modern analytical technologies to the study of the molecular basis of neurodegeneration.

Please tell us about the laser ablation-inductively coupled plasma-mass spectrometry (LA–ICP-MS) method you use in your research. Why did you decide to use that method?

LA–ICP-MS is not a new technique; many geological laboratories use this technique for studying the trace metal content of rocks without the need for complex and hazardous chemical digestion. ICP-MS is unrivaled in terms of sensitivity, so it was the logical choice for studying trace metals in the brain, and the precise optics and micrometer-scale measurement capacity of the systems make it an ideal tool for imaging metals approaching the cellular level of detail.

What are the implications of your research?

Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s), yet we know relatively little about how and why this disease occurs. More and more evidence is pointing toward mishandling of metals in dopamine-producing neurons, which produces a unique chemical reactivity toxic to the cell. By identifying the deficits in metal metabolism, we uncover new clues about why Parkinson’s disease occurs, and how we might be able to intervene therapeutically.

Do you think the results of your research will lead to a cure or better treatment for Parkinson’s disease in the future?

I think as part of a wider group, absolutely. Finding an appropriate and effective treatment for Parkinson’s requires chemists, pharmacologists, cell biologists, and biochemists, to name just a few. I do hope that, as a result of the work being carried out in my lab and numerous others around the world, an effective treatment for Parkinson’s disease is not far away.

Your current research is on studying new techniques for imaging metals in single brain cells. What kind of discoveries have you made so far?

For some time, most of my work focused on technical aspects of LA–ICP-MS analysis; how to improve image quality, how to image smaller areas, how to represent metals in the brain in three dimensions, and what not. Now, I’m working much more closely with neuroscientists to answer specific biological questions. We’re currently finding exciting new features of the healthy brain that give clues as to why only a very specific region of the brain is affected. We think that the very nature of iron in the brain as a mediator of many chemical reactions might also contribute to neurotoxicity in Parkinson’s.

What are the next steps in your work?

The next step is to examine how iron changes in the human brain in Parkinson’s sufferers. Within the confines of a laboratory is one thing, but the immense variability and environmental factors influencing iron levels in the brain presents another significant challenge to deducing the role of this essential element.

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