Highlights

  • NP exposure triggers learning and memory impairments in rats, however, NMN (the equivalent to 600 mg per day for humans) restores cognitive function.
  • NMN likely rescues cognition by increasing the quantity of memory-associated receptors — serotonin receptors — in a learning and memory-related brain region, the hippocampus.

Banned in the European Union, the hazardous compound NP is an ingredient found in dishwashing and laundry detergents. High dosage exposure to NP can cause reproductive damage from stimulation of estrogen receptors, and accumulating evidence suggests it impairs cognition. It’s not well understood how much exposure to NP most people outside the European Union undergo. Furthermore, no current cognition-preserving remedies have been identified for those with high exposure.

Published in Food and Chemical Toxicology, Liu and colleagues from the South China Agricultural University show that NP exposure drives learning and memory impairments in rats but that low-dosage NMN restores cognition. NMN increases the quantity of learning associated receptors called serotonin receptors in a brain region with key roles in learning and memory, the hippocampus. These findings suggest that NMN can help prevent cognitive decline for those exposed to high levels of NP.

NMN Reverses Nonylphenol-Induced Cognitive Impairment by Restoring Serotonin Receptors

To test whether NMN can alleviate learning and memory impairments following NP exposure, Liu and colleagues measured cognition in NP exposed rats along with those also treated with NMN. Testing the rats’ cognitive function involved a passive avoidance test that takes advantage of rat proclivity to avoid lighted areas. The researchers placed the rats into a compartment with light where they had the option to relocate to a dark compartment. The catch for the rats was that they received a foot shock when trying to walk into the darkened compartment. Thus, the longer it took the rats to walk to the darkened compartment (step-through latency), the better their fear-based memory of the foot shock.

Interestingly, NP exposure drastically reduced the step-through latency, an indicator of impaired learning and memory. Adding low-dose NMN treatments to the NP exposure restored step-through latency durations, indicative of improved learning and memory. These findings suggest that taking NMN can help prevent cognitive impairments from NP exposure.

Effects of Low-Dose NMN Treatment on NP-Induced Cognitive Impairments: Step-through latency in healthy rats (C) compared to rats exposed to NP (NP) shows a significant reduction. However, low-dose NMN treatment (NL) restores the step-through latency, indicating rescued fear-based learning and memory. Neither medium dose NMN (NM) nor high dose NMN (NH) confer significant cognitive restoration.
(Huang et al., 2023 | Food and Chemical Toxicology) Low-dose NMN treatments reversed NP-induced cognitive impairments. Compared to healthy rats (C), NP exposure (NP) significantly reduced step-through latency. Low dose NMN (NL) restored the step-through latency, indicating rescued fear-based learning and memory. Neither medium dose NMN (NM) nor high dose NMN (NH) conferred significant cognitive restoration.

Liu and colleagues sought to find how NMN reverses learning and memory impairments in rats exposed to NP. They considered memory-associated receptors (serotonin receptors) in a brain region linked to learning and memory, the hippocampus. They measured serotonin levels in this brain region, finding that NP exposure significantly reduced serotonin receptor levels. Low-dose NMN treatment in addition to NP exposure restored levels of three types of serotonin receptors — 5-HTR1A, 5-HTR4 and 5-HTR6 — and medium and high NMN doses rescued the abundance of only one serotonin receptor type — 5-HTR1A. These findings provide evidence that low-dose NMN restores cognition by increasing the abundance of all three serotonin receptor types, while higher doses increase one serotonin receptor type. These results may help explain why low-dose NMN in addition to NP exposure significantly restored cognition, while higher NMN doses conferred a statistical trend, albeit non-significant, toward cognition restoration.

Effects of NMN Treatment on Serotonin Receptor Levels: Comparison between healthy rats (C) and healthy rats given NMN (NC) shows normal serotonin receptor levels. However, NP exposure (NP) resulted in decreased levels of all three serotonin receptor types, 5-HTR1A, 5-HTR4, and 5-HTR6. Low-dose NMN treatment (NL) restored serotonin receptor levels for all three types, while medium-dose NMN (NM) and high-dose NMN (NH) only restored levels for 5-HTR1A.
(Huang et al., 2023 | Food and Chemical Toxicology) Low-dose NMN restores the abundance of all three serotonin receptors, while medium-dose and high-dose NMN rescue one receptor type. Compared to healthy rats (C) and healthy rats given NMN (NC), lower serotonin receptor levels were shown with NP exposure (NP) for all three serotonin receptor types, 5-HTR1A, 5-HTR4, and 5-HTR6. Low dose NMN (NL) restored serotonin receptor levels for all three types, and medium dose (NM) and high dose NMN (NM) restored receptor levels for 5-HTR1A.

The Mechanism Behind NMN Restoring Serotonin Receptors Remains Uncertain

The study supports that low-dosage NMN can restore cognition following NP exposure, at least in rats. Furthermore, memory formation and retrieval associated serotonin receptor levels increased with low-dosage NMN treatments. These data beg the question of how NMN increases hippocampal serotonin receptor quantities.

The way NMN confers these benefits still remains largely unknown, but it may have something to do with sirtuin proteins. NMN increases levels of the essential pro-longevity molecule nicotinamide adenine dinucleotide (NAD+). Sirtuin proteins depend on NAD+ for their function, and with increased NAD+ from NMN treatments, sirtuins may activate certain proteins called transcription factors that regulate the activation of various genes. Along those lines, it’s possible that through sirtuins, NMN increases the activation of genes coding for serotonin receptors.

We still need more research to uncover NP-associated reproductive damage and cognition impairment in humans. In that light, NMN may help counter NP’s deleterious side effects, especially as they relate to cognitive function.

NMN can be obtained for between $40 and $80 for a month’s supply taken at 250 mg per day. The study’s low dosage treatment of 125 mg/kg was the most successful in restoring cognition. At the same time, 125 mg/kg per day is equivalent to about 600 mg per day for a human weighing 165 pounds, which isn’t necessarily considered low for humans. Thus, for the same cognition-preserving effects, humans may need to take around 500 mg or more of NMN per day.