A researcher at New York Institute of Technology College of Osteopathic Medicine (NYITCOM) has secured a grant from the National Institutes of Health (NIH) to study how certain brain cells respond to chronic stress. The project is estimated to receive $1.6 million over five years and could help to identify breakthrough treatments for clinical depression, which affects more than 260 million people worldwide.
Dopamine, often referred to as “the motivation molecule,” is released from nerve cells when the brain anticipates a certain reward, signaling it to command behaviors that ensure a pleasant experience or avoid harm. When the brain associates a behavior with this reward, dopamine is also released in future scenarios, reinforcing the behavior. This habit-forming cycle, known as the reward system, motivated prehistoric humans to perform activities that met their daily needs, such as finding food. Today, dopamine signaling is often suppressed in patients with clinical depression, suggesting that dopamine imbalance causes certain behavioral symptoms, including lack of motivation. However, little is known about how the brain regulates dopamine.
Now, a research team led by Weikang Cai, Ph.D., assistant professor of biomedical sciences at NYITCOM, contends that brain cells called astrocytes play a key role in dopamine regulation. Cai and team theorize that astrocytes release the molecule adenosine triphosphate (ATP), which carries messages to nerve cells, enhancing dopamine production. During stressful situations, this astrocyte-nerve cell communication may be lost, inhibiting dopamine production and contributing to the development of major depressive disorders. If this theory holds true, findings could help to identify new treatments for these conditions. Interestingly, Cai has previously shown that insulin stimulates astrocytes to release ATP, an act that is often impaired in diabetes patients. Accordingly, this new study may also explain why these patients are prone to depression.
Joined by NYITCOM’s Randy Stout, Ph.D., assistant professor of biomedical sciences, and Emmanuel Pothos, Ph.D., associate professor at Tufts Medical School, Cai will test the theory in mice with astrocytes that are unable to release ATP. The team will monitor for correlations between ATP levels and dopamine signaling, as mice experience mild, but aversive and unpredictable environmental stressors, such as abnormal lighting and background noises. The researchers will also observe whether mice display a lack of motivation when astrocytes cannot initiate the process that ultimately enhances dopamine release. In other words, the animals’ behavior will likely mirror that of humans with clinical depression.
“We hope these studies provide new insight into the neural processes that contribute to major depressive disorders, as well as identify novel therapeutic treatments to help prevent and treat clinical depression,” says Cai. “Identifying new treatments is particularly important because not all available medications are effective for patients living with depression, despite the prevalence of the condition and its tremendous social and economic burden.”
The NIH, part of the U.S. Department of Health and Human Services, is the largest biomedical research agency in the world. First-year funding for this project totals $327,572. This grant was supported by the National Institute of Mental Health under Award Number R01MH125903. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Kim Tucker Campo