Why This Matters to Us:
As longevity enthusiasts, studies like this are crucial because mental health is directly linked to quality and longevity of life. Depression not only affects daily life and wellbeing but also has long-term implications on physical health, including increased risk for dementia. Understanding potential interventions like NMN that may alleviate depressive symptoms provides valuable insights into enhancing overall health and extending lifespan.
The Details:
Researchers have demonstrated that NMN (nicotinamide mononucleotide) can mitigate depressive-like behaviors in mice subjected to chronic social defeat stress (CSDS). Here’s an in-depth look at how NMN works and why this matters.
NMN Prevents Depressive-Like Behavior from Social Stress
Researchers created a depression model in mice by introducing social defeat stress (SDS). This involved placing a test mouse—dubbed the intruder—into the territory of a larger, aggressive mouse. This led to the intruder mouse being attacked and experiencing social defeat. After 10 days of CSDS, these mice displayed depressive-like symptoms such as social avoidance, lack of pleasure, and despair. However, when these mice were pre-treated with 100 mg/kg of NMN for three weeks, these behaviors were notably lessened.
Social Avoidance
To measure social avoidance, mice were first placed in an unfamiliar environment with a small empty cage. Their movements were tracked for 2.5 minutes. An aggressor mouse was then introduced into the cage for another round of tracking. The less time the mice spent near the aggressor's cage, the higher their social avoidance. Mice exposed to CSDS spent less time interacting with the aggressor, but mice treated with NMN maintained normal levels of social interaction.
Lack of Pleasure (Anhedonia)
Anhedonia, or lack of pleasure, was tested through the mice’s preference for sucrose (sugar water). Normally, mice prefer sweetened water over plain water. However, mice under stress often lose this preference. Under CSDS, stressed mice did not prefer sugar water, but those treated with NMN continued to enjoy the sweet water, indicating preserved pleasure response.
Despair
To assess despair, researchers used the tail suspension test, which involved suspending mice by their tails. Typically, mice will try to escape this situation, but depressed mice give up and remain immobile. Mice subjected to CSDS showed increased immobility, while those treated with NMN displayed normal escape behaviors, demonstrating reduced despair.
Can Early Life NMN Deter Depression and Dementia?
Early or middle-aged onset depression increases the risk of dementia later in life. Preventing or mitigating depression throughout life could potentially reduce dementia risks in old age. Previous studies have shown that NMN can reduce depressive-like behavior in mice. Additionally, NAD+ therapy alleviated symptoms in 93% of depressive patients in another study, implying that NMN could have similar benefits in humans. Thus, NMN not only might help combat depression but also possibly lower dementia risk.
The New Biology of Depression
For decades, depression was primarily thought to stem from a lack of neurotransmitters like serotonin and norepinephrine. However, this view is evolving. The mitochondrial hypothesis suggests that defective mitochondria are a source of depression. Mitochondria generate ATP, the cell’s energy currency, and the brain has the highest energy demand of any organ. In depressed patients, mitochondria in areas like the frontal cortex are often dysfunctional and lack Complex I, a critical protein for energy production. This dysfunction leads to increased reactive oxygen species (ROS), causing cellular damage, reduced ATP production, and cell death, contributing to depressive symptoms.
Conclusion
NAD+ helps in ATP production by interacting with Complex I in mitochondria. Increasing NAD+ levels with NMN could enhance mitochondrial function, reduce ROS, and consequently mitigate depressive symptoms. By promoting mitochondrial health, NMN might not only improve mental health but also contribute to overall longevity and enhanced quality of life.
This article provides an overview of the study in a user-friendly format, explaining the importance of NMN in combating depressive symptoms and highlighting its relevance to overall health and longevity. If you have more studies or specific topics, feel free to share!
