Deficient ATP release in the brain drives depressive- and anxiety-like behaviors

In a new JNeurosci paper, Tian-Ming Gao and colleagues, from Southern Medical University, explored how adenosine triphosphate (ATP) signaling relates to depression and anxiety using male mice. ATP is a molecule that not only provides energy but also supports communication between neurons. The researchers focused on ATP signaling in a brain region implicated in depression called the hippocampus. 

Male mice that were more likely to acquire depressive- and anxiety-like symptoms following long-term stress had less ATP levels and reduced expression of a protein involved in ATP release (connexin 43). When the research team genetically dampened or deleted connexin 43 in cells that release ATP in another group of mice, this alone led to depressive- and anxiety-like behaviors and lowered ATP levels. Bridging the findings together, in distressed mice, restoring connexin 43 in the hippocampus brought ATP levels up to normal and improved behavioral outcomes. 

This is the first direct evidence that deficient ATP release in [a region of the] hippocampus drives both depressive- and anxiety-like behaviors, revealing a shared molecular pathway [for these conditions]."

Tian-Ming Gao, Southern Medical University

Gao also emphasizes that the findings linking connexin 43 to this mechanism point to a potential treatment target for treating depression and anxiety when they occur at the same time. Of note, the researchers plan to assess both sexes in future studies.