NEW FACES

USC School of Pharmacy research shows broader potential of drug that shields the liver from effects of alcohol use.

After previously demonstrating how dihydromyricetin (DHM) shields the liver from effects of alcohol use, USC School of Pharmacy faculty members Jing Liang and Daryl Davies are now shedding light on its potential to protect the brain from dementia. This research is especially timely, given the long-term effects of COVID-19 lockdowns. The resulting social isolation led to increases in anxiety disorders that are expected to continue long after the pandemic recedes into history.

This rising prevalence is itself a cause of worry, the researchers note, as anxiety disorders already account for nearly a third of our nation’s mental health spending. And the long-term effects of anxiety can include the cognitive decline associated with Alzheimer’s disease and other dementia disorders—which are also escalating in incidence.

“Social isolation heightens stress and anxiety, which contribute to neuroinflammation,” Liang says. In turn, neuroinflammation, which stems from the brain’s attempts to protect the central nervous system, is a driving factor in Alzheimer’s and other neurodegenerative conditions.

“Even though anxiety-reducing medications are available, they can have substantial side effects and often fail to overcome treatment resistance or prevent relapse,” adds Davies, director of the Alcohol and Brain Research Laboratory, and one of the leaders of the new USC Institute for Addiction Science.

Microglia, the resident macrophages of the brain’s innate system, are key players in modulating the neuroinflammatory response in the central nervous system, Liang says. “Microglia are not only involved in nervous-system infection and debris phagocytosis but also play a crucial role in the physiological development of the brain by engaging in the shaping process of neuronal circuits and synapse plasticity,” she adds.

Homing in on astrocytes—major microglia cells that regulate brain function—as a probable mechanism in social isolation-induced anxiety, Liang, Davies and their colleagues are exploring DHM as a more effective means of stopping the condition. “Our prior research revealed DHM’s positive effects on the brain’s gamma-aminobutyric acid (GABA) receptors, which are charged with inhibiting neuronal excitability,” Liang explains. “The current work explored the hypothesis that astrocytes are involved in the pathway of GABAergic Even though anxiety-reducing medications are available, they can have substantial side effects and often fail to overcome treatment resistance or prevent relapse.”

Daryl Davies, Timothy M. Chan Professor of Complementary Therapeutics

transmission,” which activates the receptors and cognitive formation.

This research, published in the Journal of Neuroinflammation and Scientific Reports, used a trauma- and stressor-related-disorder mouse model to determine the level of neuroinflammation triggered by isolation-induced stress. “Along with deficits in cognition and memory, we found that social isolation decreased the size and complexity of astrocytes in the hippocampus,” Liang says.

Not only did administration of DHM improve cognitive and memory abilities, but it also restored the plasticity and functionality of astrocytes.

Although more studies are needed before this research can move to clinical trials, it both confirms the roles of microglia and astrocytes in isolation-induced cognitive impairment and demonstrates the potential of DHM as an effective therapy. However, note Liang and Davies’ team, early interventions will remain essential if cognitive dysfunctions and dementia disorders are to be averted.

This continuing research was supported by the National Institutes of Health. NEW FACES

Maddalena Ferranna, PhD, has joined the Department of Pharmaceutical and Health Economics as an assistant professor. She previously was a research associate at the Harvard T.H. Chan School of Public Health. Her main research interests are welfare economics, global health and climate change economics, particularly the development and application of methods to assess the equity implications of health and environmental interventions. She received a PhD in economics from Toulouse School of Economics and was a values and public policy postdoctoral fellow at Princeton University.

Dimitris Sakellariou, MBA, has joined the USC School of Pharmacy as chief operating officer, overseeing all financial and administrative operations, including ongoing evaluation, analysis and reporting of performance against strategic priorities. He was most recently assistant vice president for student affairs operations at the California Institute of Technology. He earned an MBA from the USC Marshall School of Business, a master’s degree in electrical engineering from Caltech, a master’s degree in engineering from ETH Zurich and a business process management certificate from Pepperdine University.