NC West Virginia News

West Virginia University neuroscientists have identified a method to regulate zinc release in specific brain areas. Zinc is crucial for brain function, enhancing memory and alleviating symptoms of certain neurological disorders. However, precise delivery is essential.

"Zinc is like a volume knob in many parts of the brain," stated Charles Anderson, assistant professor at the WVU School of Medicine's Department of Neuroscience and Rockefeller Neuroscience Institute. Anderson led the study, which could pave the way for pharmaceutical developments targeting various diseases.

"You can turn it a little bit up and a little bit down," he explained. "The idea was that if we could find the drugs that control that last little bit of volume, we can selectively change certain connections in the brain that have zinc and the receptors that zinc acts on."

Published in The Journal of Neuroscience, the study highlights the zinc transporter protein ZIP12's role in synaptic activity—how nerve cells communicate information. Anderson emphasized its significance in advancing understanding of synaptic zinc's roles in health and disease and how molecular compounds can modify their strength.

"It’s basically a way to fine-tune synaptic transmission," Anderson noted.

Research indicates that zinc levels and receptor sensitivity influence synaptic connection strength or weakness. Altered synaptic zinc signaling has been linked to conditions like autism, schizophrenia, and Alzheimer’s disease.

"There are several neurological conditions associated with changes in these zinc transporter proteins," Anderson said. "For example, when we profile people who have schizophrenia versus healthy people, we find extra zinc transporters expressed in the brains of people with schizophrenia. If we could make a drug that reduces the function of that zinc transporter, that might help turn their system back down to the level of a healthy person."

The research builds on Anderson’s studies on neuron-to-neuron zinc release—its actions and duration.

"These are three fundamental basic features of zinc signaling," he said. "That gives us an outline of what’s possible when we think about how the brain could take advantage of the systems it can use to modulate strength."

Anderson's team needed tools to block and activate different parts of this system. They screened molecular compounds interfering with proteins involved. Philip Bender, WVU alumnus and postdoctoral fellow from Morristown, New York, conducted experiments using these compounds on brain tissue to assess changes in synaptic function.

"The major importance of this study is the identification of a family of compounds which could potentially lead to therapeutics for a wide range of disorders as the transporters targeted have tissue-specific functions," Bender said.

Collaborating with Anderson were Abbey Manning; Benjamin Z. Mendelson; Kaitlin Bainer; Rayli Ruby; Victoria R. Shifflett; Donald Dariano; Bradley A. Webb; and Werner J. Geldenhuys—all affiliated with WVU School departments.

Anderson hopes these findings offer scientists tools to better understand protein contributions to brain function. He plans future studies on zinc's role in sensory processing—a key therapeutic consideration for neurological conditions.