Tier 3 — preclinical

Nicotinamide mononucleotide stimulates the activity of bursting slow-oscillation neurons in the supramammillary nucleus and enhances REM sleep

Youssouf Cissé, Cynthia S Brace, Virginia Hsu, Carla M Yuede, Nicholas Rensing, Michael Wong, Shin-Ichiro Imai
iScience 2026 29(5):115741

Bibliography

PubMed
PMID 42170103
PubMed Central
PMC13187527
DOI
10.1016/j.isci.2026.115741

Study snapshot

DesignMechanistic mouse study using juxtacellular recording, Slc12a8-deficient mice, optogenetics and chemogenetics to interrogate sleep circuitry.
ModelYoung and aged mice, including Slc12a8-deficient animals.
SamplePreclinical mouse neurophysiology study; no human participants.
InterventionNMN administration with electrophysiologic and circuit-manipulation experiments targeting supramammillary GABAergic neurons.
DurationAcute and age-comparison experimental protocols; no human supplementation duration.
EndpointsREM sleep; Supramammillary bursting slow-oscillation neuronal firing; Theta power; Novel object recognition; Response to Slc12a8 deficiency; Optogenetic/chemogenetic circuit effects

What the study showed, in plain terms

This 2026 study identified a specific brain circuit through which NMN can influence REM sleep in mice. Aged mice had reduced activity of bursting slow-oscillation neurons in the supramammillary nucleus, and NMN restored their firing toward younger levels.

Mice lacking Slc12a8 showed impaired NMN responses, reduced REM theta power and worse novel-object recognition, while direct circuit manipulation changed REM sleep.

The study is useful mechanistic evidence for NMN and sleep, but it does not show that an NMN supplement treats insomnia, improves human REM sleep or enhances memory in people.

Key findings

  • Aged mice showed reduced firing of REM-active supramammillary bursting slow-oscillation neurons.
  • NMN restored neuronal activity toward levels seen in younger mice and enhanced REM sleep in the model.
  • Slc12a8 deficiency impaired NMN response and reduced REM theta power.
  • Circuit manipulation supported a causal role for the identified supramammillary GABAergic pathway in REM sleep.
  • No human participants were studied.

What this study can and cannot tell us

This is a mouse study and does not establish a clinical sleep benefit from oral NMN in humans.

The work investigates a specific neural mechanism rather than insomnia, sleep-apnea treatment, fatigue or long-term patient-important outcomes.

Dose and brain exposure in experimental mice cannot be mapped directly onto consumer NMN dosing.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology