A new study suggests that a single molecular deficiency in the brain’s energy signaling system may be a common cause of both depression and anxiety.
A groundbreaking study conducted by Tian-Ming Gao and colleagues from Southern Medical University has shown how adenosine triphosphate (ATP) signaling triggers factors such as depression and anxiety in male mice.
Adenosine Triphosphate (ATP) is known as the cell’s main energy source, but it also acts as a neurotransmitter that helps neurons communicate effectively.
The healthy communication between brain cells is crucial for managing emotions, because the researchers focused their work on the hippocampus, a region specifically involved in memory, stress responses and the onset of despondency.
Central role of Connexin 43 to maintain brain energy health
The researchers analyzed that male mice are prone to developing depressive and anxiety-like behavior after prolonged stress and energy depletion.
These mice also produced less of a key protein needed for ATP release.
Connexin 43 has been observed to form channels that allow ATP to navigate between certain cells, making it an important part of how the brain maintains healthy energy and signaling levels.
To investigate whether reduced ATP release caused mood-related symptoms, the team genetically reduced connexin 43 in cells that normally release ATP.
To test whether reduced ATP release resulted in mood-related symptoms, the team removed connexin 43 from cells that normally release ATP.
The same experiment was performed on another group of mice that had not been exposed to longer periods of stress.
The results showed that even without a high-stakes situation, lowering levels of connexin 43 activated depressive-like behavior and lowered ATP levels.
Research results further suggested that interference in ATP release alone could influence emotional behavior.
This recovery underlines the idea that ATP plays a crucial role in modulating mood.
Regulatory pathway for depression and anxiety
This marks the first evidence that ATP depletion in the hippocampus causes both depressive and anxiety behaviors, revealing a shared molecular pathway for such conditions.
This revelation is critical because coexisting depression and anxiety can be difficult to treat concurrently with prior therapies.
The research team was able to develop interventions to simultaneously address the conditions.
It also plans to integrate both male and female mice to analyze whether these mechanisms work in the same way, as the future of understanding disorders lies not only in the neural circuits, but also central to the brain’s cellular energy health.
