Key Points
- NMN significantly restored brain NAD⁺ levels
- Improved BBB structure and reduced permeability
- NMN improved behavioral outcomes
- Mitochondrial function was improved
Overview of Methods
Adult male mice were assigned to three groups, two of which were exposed to environmentally relevant DBP for 28 days:
- Control group: placebo
- DBP group: 500 mg/kg DBP
- DBP + NMN group: 500 mg/kg DBP plus 300 mg/kg NMN
Researchers evaluated BBB function, molecular signaling pathways, inflammation, neuronal damage, and behavioral performance.
NMN Preserved Blood-Brain Barrier Integrity
DBP suppressed the expression of proteins that maintain BBB structure and regulate inflammatory signaling.
NMN reversed these effects, restoring expression of proteins involved in barrier maintenance, cellular stress resistance, and inflammatory control.
"NMN administration exerted therapeutic effects on DBP-induced BBB damage by reversing the expression levels of ZO-1, Occludin, Sirt1 and FOXO1a."
Evans Blue dye leakage, a marker of blood-brain barrier permeability, was reduced, indicating improved barrier tightness and vascular protection.
"NMN treatment significantly reduced Evans Blue dye extravasation and restored neuronal structure in the cerebral cortex."
Markers of neuroinflammation and neuronal damage were elevated in DBP-exposed mice. NMN lowered inflammatory signaling and protected neurons from injury.
"NMN treatment led to a reduction in pro-inflammatory cytokine levels, indicating an amelioration in neuroinflammatory responses."
NMN uptake, intracellular transport, and systemic NAD+ regulation govern stress resistance pathways that support vascular and barrier integrity under toxic and inflammatory conditions.
Improved Cognitive and Behavioral Outcomes
DBP exposure impaired learning and memory performance in mice. NMN supplementation improved cognitive and behavioral outcomes, aligning with restored BBB and reduced neuroinflammation.
"NMN effectively ameliorates DBP-induced cognitive deficits by reducing hippocampal neuronal loss and restoring behavioral performance."
Overall behavioral performance was consistently improved with NMN treatment.
"Behavioral metrics revealed marked cognitive enhancement… indicating robust spatial memory restoration."
"NMN treatment elicited quantifiable behavioral improvements."
Conclusion
This study demonstrates that NMN restores NAD⁺ levels in the brain, improving protein expression and cellular signaling pathways associated with BBB maintenance. NMN treatment reduced BBB permeability, limited neuroinflammation, and supported improved behavioral outcomes.
"NMN mitigates DBP-induced BBB disruption by replenishing NAD+ levels and reactivating the Sirt1/FOXO1a pathway, thereby reducing neuroinflammation."
"NMN-driven NAD+ replenishment effectively mitigates phthalate toxicity and restores neurovascular integrity."
Comprehensive reviews of NAD⁺-targeted therapies show how restoring NAD⁺ can simultaneously influence neuroinflammation, vascular integrity, mitochondrial health, and neuronal survival across diverse brain injury models.
Together, these findings support NAD⁺ restoration as a promising strategy for protecting neurovascular health against environmental toxins and inflammatory stressors.
