Recent research has provided exciting new insights into the role of astrocytes, the star-shaped cells in the brain, in regulating stress responses. This discovery may pave the way for innovative treatments for mental health conditions such as anxiety and depression. Traditionally, astrocytes were believed to serve a supportive function, primarily providing structural and metabolic support to neurons. However, recent findings have highlighted their active involvement in complex brain functions, including the regulation of stress in the brain’s lateral septum.
When the body encounters stressful or threatening stimuli, a cascade of physical responses is triggered. These responses include the release of stress hormones, activation of the sympathetic nervous system, and behaviors designed to avoid or manage the threat. While these mechanisms are adaptive in the short term, prolonged or excessive stress can lead to a range of health problems, including neuropsychiatric disorders like anxiety, depression, and post-traumatic stress disorder (PTSD).
The lateral septum, a region of the brain that plays a pivotal role in regulating emotional responses such as fear, anxiety, and social behaviors, has long been studied in relation to stress. For years, research focused primarily on neurons as the central players in these processes. It was unclear, however, how astrocytes contributed to the regulation of stress, despite their abundant presence in regions like the lateral septum. This gap in knowledge has now been addressed by a groundbreaking study led by Prof. Lee Hyo-sang, a neuroscientist at the Department of Brain Sciences, DGIST, in collaboration with Prof. Choi Sae-Young from Seoul National University School of Dentistry.
In their experiments with rats, Prof. Lee’s team discovered that astrocytes in the lateral septum are not passive cells but actively respond to stress-inducing stimuli. When exposed to stress, the intracellular calcium concentration within astrocytes increased significantly, signaling a cascade of events that influence surrounding nerve cells. One of the key findings was the release of adenosine, a signaling molecule that interacts with neighboring neurons. This adenosine release suppresses the activity of these neurons, thereby modulating the brain’s response to stress.
What makes this discovery particularly intriguing is the team’s observation that astrocytes may respond differently depending on the nature of the stressor and their specific location in the brain. This suggests that astrocytes play a dynamic and nuanced role in managing stress, rather than merely being passive mediators of neuronal activity. Additionally, the research revealed that astrocytes might regulate stress responses in a more targeted and region-specific manner, influencing how different brain circuits respond to different types of stressors.
This research offers the first detailed molecular explanation of how astrocytes sense stress and interact with neurons to regulate stress responses. Understanding these interactions at the molecular and neural circuit levels is crucial for developing more precise therapeutic approaches. By illuminating the specific mechanisms by which astrocytes affect the brain’s stress circuits, the findings provide new avenues for research aimed at mitigating the harmful effects of chronic stress and its related disorders.
One of the most exciting implications of this study is its potential to inform the development of new treatments for mental health disorders. Current treatments for anxiety, depression, and related conditions often target neurotransmitters or neuronal pathways, but they can be limited in effectiveness and may come with undesirable side effects. By targeting the interaction between astrocytes and neurons, new therapies could offer a more targeted approach to modulating the brain’s stress circuits. This could involve developing drugs or technologies that regulate the release of adenosine or other signaling molecules involved in astrocytic communication.
Prof. Lee emphasized the significance of the study, noting that it reveals the key role of astrocytes in regulating stress and emotional responses. “Through this study, we have learned that astrocytes play a key role in stress and emotion regulation,” he said. “We hope to contribute to the development of treatments for mental disorders based on this research.” The ability to target astrocytes could not only provide more effective treatments for stress-related disorders but could also lead to therapeutic strategies that are more precisely tailored to individual needs, improving the overall efficacy and safety of mental health interventions.
The collaboration between Prof. Lee’s team at DGIST and Prof. Choi’s team at Seoul National University School of Dentistry highlights the interdisciplinary nature of this research. Combining expertise in brain science and dentistry, the teams were able to explore the molecular and neural mechanisms that underlie stress responses and emotional regulation. This collaborative approach is crucial for advancing our understanding of the brain and finding innovative ways to treat complex disorders.
The study was published in Nature Communications on November 21.