Cell communicator involved in brain dysfunction

By John Murphy, MDLinx
Published January 5, 2016

Key Takeaways

A small molecule commonly found “decorating” brain cells in humans and other higher animals may affect brain structure and function, according to research from neuroscientists at The Johns Hopkins School of Medicine in Baltimore.

The molecule is sialic acid, and small errors in how it attaches to cell surfaces can cause damaged brain structure, poor motor skills, hyperactivity, and learning difficulties in mice, the researchers found.

Their findings, which appear in the July 2015 issue of The FASEB Journal, recognizes that sialic acid plays a significant role in intermolecular and intercellular interactions. Further, changes in sialic acid attachment may shed light on the underlying causes of certain brain disorders in humans.

“Sialic acid is part of the molecular language that cells use to communicate among themselves,” says Ronald Schnaar, PhD, a professor of pharmacology and neuroscience at the Johns Hopkins University School of Medicine. “As we learn that language, we can use the knowledge to better understand disease and perhaps thoughtfully intervene.”

To make their discovery, Dr. Schnaar and colleagues mutated mouse genes responsible for sialic acid attachment, and then compared the brain structure, motor functions, activity, and learning in the deficient mice to those of normal mice. They found that the mice with altered sialic acid attachment had a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier.

When compared to normal mice, the experimental mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability.

“The molecular codes that control the human brain are as yet poorly worked out,” said Gerald Weissmann, MD, editor-in-chief of The FASEB Journal. “This report shows how small molecules, such as sialic acid, direct cell communication to profoundly affect behavior. With this information, researchers have new ways to work out the mechanisms that determine hyperactivity and other brain disorders.”

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