Research Offers New Clues on How Manganese Enters Brain

Brittany L. Steimle received the award for outstanding poster for her presentation at the international Trace Elements in Biology and Medicine science research conference sponsored by the Federation of American Societies for Experimental Biology (FASEB) in June in Tahoe City, California.

Steimle is a doctoral candidate in biochemistry and a former student of the PhD Program in Biomedical Sciences.

Her poster, titled “The Regulatory Mechanisms of Manganese Flux Into the Brain Via the Blood-Brain Barrier,” outlined how proteins transport manganese in the brain.

Steimle conducts research in in the laboratory of Daniel J. Kosman, PhD, SUNY Distinguished professor of biochemistry, where the focus is on the regulation of manganese and other essential nutrients in the brain. 

She explains that manganese is essential for bone formation, brain development and metabolizing carbohydrates, cholesterol and amino acids.

However, she notes, workers in the welding, mining and ore-crushing industries may be susceptible to overexposure by inhaling manganese, which can induce neurological disorders like manganism, a condition that resembles Parkinson’s disease with symptoms such as tremors, difficulty walking and facial spasms.

The similarity between the two has led to proposals that manganese may also play a role in Parkinson’s disease.

“To develop therapeutics for manganese-induced neurological diseases, we must first understand how manganese enters the brain,” Steimle says.

Her study focused on how dietary manganese crosses into the brain through the blood-brain barrier, (BBB), a largely impermeable barrier that regulates passage of nutrients into the brain.

Brain microvascular endothelial cells make up the basis of the BBB through the formation of tight junctions between endothelial cells.

“Due to the restrictive nature of this barrier, nutrients can only pass into the brain through transporters and chaperone proteins expressed by these endothelial cells,” Steimle says.

“Our objective is to characterize the transport systems that regulate manganese uptake into the brain and to further investigate how such mechanisms protect against manganese-induced neurotoxicity.”

In Kosman’s lab, Steimle and her colleagues use an in vitro model of the BBB, developed by Ryan McCarthy, PhD, a former graduate student in the lab.

In the model, brain microvascular endothelial cells are grown under conditions that mimic the in vivo environment of the BBB.

“Understanding how manganese accumulates into the brain through the blood-brain barrier may serve as a key to designing drug targets for individuals who may have been overexposed to manganese in the environment or in whom manganese metabolism has somehow become dysregulated,” Steimle says.

The work was funded by a National Institutes of Health grant.

At the FASEB conference, Steimle was selected to present a three-minute “elevator pitch” about her research to encourage attendees to visit her poster presentation.

“This was an exceptional meeting, which brought together a wide range of scientists to discuss the impact of trace elements on human health, nutrition and disease,” she says.

Steimle notes trainees were able to discuss their work, attend career workshops and meet experts in the field.

“Overall, this conference was a great opportunity to interact with current leaders in the field, build new collaborations and develop career-building skills,” she says.