A researcher from the New York Institute of Technology College of Osteopathic Medicine got a grant from the National Institutes of Health to study how certain brain cells respond to chronic stress. The project is expected to receive $ 1.6 million over five years and could help identify breakthrough treatments for clinical depression, which affects more than 260 million people worldwide.
Dopamine, often referred to as a “motivator molecule,” is released from nerve cells when the brain anticipates a certain reward, signaling it to behaviors that ensure a pleasurable experience or prevent damage.
When the brain associates a behavior with this reward, dopamine is also released in future scenarios, reinforcing the behavior. This cycle of habit formation, 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 is causing 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, assistant professor of biomedical sciences at NYITCOM, argues that brain cells called astrocytes play a key role in regulating dopamine.
Cai and his team theorize that astrocytes release the adenosine triphosphate molecule, which transmits messages to nerve cells, improving dopamine production. During stressful situations, this astrocyte-nerve cell communication can be lost, inhibiting dopamine production and contributing to the development of major depressive disorders.
If this theory is true, the results could help identify new treatments for these conditions. Interestingly, Cai has previously shown that insulin stimulates astrocytes to release ATP, an act often altered in diabetic patients. As a result, this new study may also explain why these patients are prone to depression.
Joined by NYITCOM’s Randy Stout, assistant professor of biomedical sciences, and Emmanuel Pothos, associate professor at Tufts Medical School, Cai will test the theory in mice with astrocytes unable to release ATP. The team will monitor correlations between ATP levels and dopamine signaling, as mice experience mild, but aversive and unpredictable environmental stressors, such as abnormal lighting and background noise.
The researchers will also observe whether the mice display a lack of motivation when astrocytes cannot initiate the process that ultimately enhances the release of dopamine. In other words, the behavior of animals will likely mirror that of humans with clinical depression.
“We hope that these studies will provide new insight into the neural processes that contribute to major depressive disorders, as well as identify new therapeutic treatments to help prevent and treat clinical depression,” says Cai. “Identifying new treatments is particularly important because not all available drugs are effective for patients with depression, despite the prevalence of the disease and its enormous social and economic burden.”