Scientist seeks answers about manganese toxicity, Parkinson's disease

People exposed to manganese in occupational settings such as welding may not see signs for years that the element is toxic to their nervous systems, but new medical imaging techniques being developed and tested by a Purdue University professor could help reveal toxicity before symptoms indicating irreversible brain damage begin  to occur.
 
Ulrike Dydak, an assistant professor of health sciences who specialises in medical imaging of neurodegenerative diseases, received more than $2 million through an Outstanding New Environmental Scientist Award (ONES) from the National Institute of Environmental Health Sciences, which is part of the National Institutes of Health.
 
The five-year grant will help fund Dydak's non-invasive neuroimaging techniques using magnetic resonance imaging or MRI, to study manganese toxicity. The work could lead to a better understanding of the neural system and the mechanism of manganese toxicity, which has similarities to Parkinson's disease.
 
"Patients with manganese intoxication - also known as manganism and manganese-induced Parkinsonism - as well as patients with idiopathic Parkinson's disease, have motor control issues, tremors and problems walking," Dydak said. "However, the patients with manganism don't respond to the medication used to manage Parkinson's disease symptoms because the two conditions have a different mechanism. Early diagnosis is crucial for prevention, and our goal is to see if we can identify pre-symptomatic biomarkers through new imaging techniques to create a diagnostic tool and also learn more about the disease so patients can better manage it."
 
Those who are mostly affected by manganese intoxication work in welding or smelting in the steel industry. There also is low-level exposure from gasoline as well as the environment of steel plants. Manganese is an element that is essential to neurological function, but too much is toxic and can cause irreversible brain damage. It also has been found recently that low amounts of manganese exposure can affect cognitive functions, such as short-term memory or reaction time.
 
"So far, most studies on the toxicity of manganese and other metals are performed in animal models," she said. "If we can improve medical imaging to observe specific changes in living human brain chemistry and observe these changes over the long run, it will help create a better understanding of this neurodegenerative disease and help people by improving diagnostic and therapeutic tools."
 
Imaging techniques that can better reveal the levels and interactions of amino acids, neurotransmitters and other physiological aspects of the brain also would be of interest to those researching other neurodegenerative diseases and in fields such as psychiatry and speech, language and hearing sciences.
 
Dydak has studied welders in China, where until recently the amount of manganese exposure was less regulated. Dydak will use the grant to continue developing imaging software and to observe study participants for the long term. She also will be able to study US welders.
 
"Since it is not known at what levels of exposure manganese starts to have adverse effects, it also is important to study our local welders, even if they work under well-regulated exposure conditions," Dydak said.
 
Dydak has shown in previous studies that manganese exposure is related to an increase of the brain's main inhibitory neurotransmitter, gamma-aminobutyric acid, known as GABA. The increase occurs in a region of the brain responsible for movement. She also found that young, healthy workers exposed to manganese daily in the workplace had double the levels of GABA than control subjects. The increase in GABA was accompanied by a decrease in levels of N-acetylaspartate, which indicates decreased neural function. Her findings were published in the February 2011 Environmental Health Perspectives journal.
 
In the upcoming study, the brain chemistry and health of 48 workers with high and low exposure levels will be compared to 24 people who aren't exposed, 15 manganism patients, and 24 patients with Parkinson's disease not related to manganese exposure.
 
While the study's human component focuses on noninvasive diagnostic tools by MRI, the animal component will focus on new imaging options in positron emission tomography (PET) scans to learn more about brain chemistry. In this part of the study, Dydak will focus on changes of dopamine, which helps the brain regulate movement.
 
"In Parkinson's disease, it is known that the dopamine system is compromised," she said. "Using PET imaging and novel MRI techniques at the same time allows us to pick up and analyse changes between dopamine and GABA."
 
Dydak is working with the Guangxi Medical University in Nanning, China, and Indiana University School of Medicine. She is based in Purdue's School of Health Sciences, and her imaging lab is at the Indiana Institute for Biomedical Imaging Sciences at IU's School of Medicine, where she has a joint appointment.