Past research has found that patients with major depressive disorder have reduced production of the energy molecule adenosine triphosphate (ATP). This reduced ATP production may stem from dysfunction of the cell's power plants, the mitochondria, and is thus linked to depression.
Improving mitochondrial function may be an intervention to improve depression-like behaviors. As a key molecule that keeps the energy production line running, boosting NAD+ with precursor molecules like NMN should boost mitochondrial function.
The research team at Zhejiang University of Technology found that cortisol-induced depression reduced NAD+ levels in the brains of mice, but NMN treatment restored NAD+ levels. What's more, they found that NMN injections enhanced mitochondrial energy production in the brain. They believe this is related to the ability of NMN treatment to reverse depressive behavior.
To study the interaction between NMN and depression, the researchers induced depression in mice by injecting a stress hormone, cortisol. After four weeks of stress hormone injections, the researchers added NMN to the injections for the next two weeks.
When the researchers assessed the mice for their performance, they found that the NMN-treated mice exhibited less depression-like behavior than untreated mice. They used something called the "forced swim test" to measure depressive behavior. Healthy mice generally struggled to stay afloat, while "depressed" mice gave up swimming earlier.
The researchers found that mice that received cortisol and NMN injections began swimming longer in the tank to survive than mice that received only cortisol injections or were not treated at all. These results show that NMN can alleviate depressive behavior in mice.
The researchers also looked at the activity of proteins that regulate cellular energy production and depend on healthy NAD+ levels to function. They examined a protein, SIRT3, that is critical for regulating mitochondrial health. Under the induction of depression, the level of SIRT3 disappeared, but could return to normal level after NMN treatment.