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Key Points
- Wood smoke impaired brain chemistry and behavior
- Resveratrol + NMN provided the strongest protection
- Combination therapies showed mixed results
- NAD+ proved to be a key target for protecting the brain from pollution
Methods
60 female mice aged 18 months were split evenly into 10 groups and exposed to either filtered air (FA) or wood smoke (WS) for 4 hours every other day for 14 days (7 total exposures)
Treatment Groups:
After exposure, two groups (one FA, one WS) were euthanized 24 hours later to assess immediate effects. The remainder were treated for 10 weeks with:
- Placebo (control): Normal food and water, placebo gavage
- RNMN (resveratrol + NMN): ≈167 mg/kg/day resveratrol in food & ≈300 mg/kg/day NMN in water
- DQ (dasatinib + quercetin): 5 mg/kg dasatinib & 10 mg/kg quercetin three days per week, every other week, for 10 weeks through gavage
- RNDQ (RNMN + DQ): combination of the RNMN regimen with the intermittent DQ schedule
NMN + Resveratrol Prevented Wildfire Smoke–Induced Drops in Brain NAD⁺ and Serotonin
WS exposure led to a sharp decline in levels of NAD⁺ within the prefrontal cortex (PFC), a key brain region for mood and decision-making.
"At 24 h post-exposure… a significant reduction in NAD⁺ within the prefrontal cortex was observed… NAD⁺ concentrations remained significantly reduced in WS-exposed mice 10 weeks after exposure."
Levels of serotonin (the neurotransmitter essential for mood and stress resilience) were also reduced.
"Serotonin levels were significantly decreased in WS-exposed mice immediately after exposure and remained reduced at 10 weeks post-exposure."
Resveratrol, together with NMN, (RNMN) not only restored NAD⁺ levels in the prefrontal cortex but also brought serotonin concentrations back toward normal.
"RNMN treatment restored NAD⁺ concentrations in the prefrontal cortex… Serotonin concentrations, significantly reduced in WS-exposed mice, were normalized by RNMN treatment."
Inflammation Triggered by Wood Smoke Reduced by RNMN
Wood smoke exposure also triggered signs of hidden inflammation in the brain, showing higher levels of two proteins (NLRP3 and caspase-1) that are closely linked to brain inflammation and aging.
"NLRP3 and caspase-1 protein levels were significantly elevated in WS-exposed mice at 10 weeks post-exposure compared to controls… These data indicate persistent elevation in inflammasome priming, but lack of overt cytokine maturation and release in the brain."
RNMN reduced NLRP3 and caspase-1 expression, lowering inflammation and restoring a healthier brain environment.
"RNMN-treated mice… lowered [inflammatory] NLRP3 and caspase-1 expression, attenuating inflammasome priming at 10 weeks post-exposure."
RNMN Improved Behavior and Stress Resilience
WS exposure led to depressive-like behavior, with mice giving up sooner in the forced swim test, though grip strength was unchanged.
"Immobility time in the forced swim test was significantly increased in WS-exposed mice compared with controls, while grip strength did not differ between groups."
RNMN treatment reduced immobility, improving stress resilience and behavior.
"RNMN-treated mice displayed significantly less immobility in the forced swim test compared with untreated."
Conclusion
This study shows that even short-term exposure to wood smoke can have lasting effects on brain health and behavior, especially during periods of high smoke exposure.
Treatment with RNMN not only reduced these effects but actively restored brain health and behavior, showing real promise to protect or restore brain function when the brain is stressed by environmental pollutants. These findings add to growing evidence that NMN supplementation can protect against various forms of air pollution damage.
"NAD⁺ and serotonin reductions, elevated inflammasome markers, and behavioral alterations persisted for 10 weeks following subacute WS exposure…"
"RNMN treatment resolved WS-induced reductions in NAD⁺ and serotonin, reduced immobility in the forced swim test, and lowered neuroinflammatory markers."
While more research is needed to fine-tune how resveratrol and NMN each contribute, and to ensure safety in humans, this provides a foundation for using anti-aging interventions to defend the brain against everyday pollutants and preserve healthy aging.
"Taken together, these findings highlight that subacute (14-day) exposure to WS results in persistent neurometabolomic and behavioral alterations in an aged mouse model and that intervention with RNMN may be a useful strategy to mitigate the adverse neurological outcomes observed."
