Grant will fund study of meth neurotoxicity

With more than 35 million users worldwide, methamphetamine (meth) is one of the most common and puzzling illicit drugs used today.

“Meth abuse poses a significant health threat. It acts on almost every organ in the body, including the brain, and can significantly impact function at even the cellular level,” said Sowmya Yelamanchili, Ph.D., an assistant professor in the UNMC Department of Pharmacology and Experimental Neuroscience.

Dr. Yelamanchili is particularly interested in learning more about the inflammation meth causes in the brain and why it has such a profound effect on overall brain function.

To learn more about the mechanism underlying meth neurotoxicity, Dr. Yelamanchili was awarded a $1.7 million grant from the National Institutes of Health.

Her research focuses specifically on cell communication in the central nervous system. In this study, Dr. Yelamanchili will study the chronic effects of meth on secretion of extracellular vesicles and changes associated with the microRNA cargo these vesicles carry that subsequently results in synaptic changes and neuronal injury in the brain.

MicroRNAs play a role in suppressing gene expression. A certain group of microRNAs also bind to toll-like receptors, which are involved in a plethora of cellular processes.

The emphasis in Dr. Yelamanchili’s study is on the microRNA’s role in eliciting neuronal damage, she said.

This work also stems from her previous studies in SIV encephalitis, another NIH-funded collaborative grant with Howard Fox, M.D., Ph.D., also a professor in the Department of Pharmacology and Experimental Neuroscience.

“What are the molecular stories behind this phenomenon? Why does meth affect males and females differently? And what happens in co-morbid conditions such as HIV infection?” Dr. Yelamanchili asked.

These and other questions are ones she will study over the next five years of the grant.

“We know meth impacts the biogenesis of extracellular vesicles in the brain and changes the microRNA, we just don’t understand how or why, and that is what we hope to discover,” she said.