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Study · Animal study (in vivo) · mouse · 2018

2 results

CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves.

Johnson S, Wozniak DF, Imai S

NPJ aging and mechanisms of disease8 Nov 2018Cited by 49 (Europe PMC)

PMID30416740 (opens in a new tab)PMCIDPMC6224504 (opens in a new tab)DOI10.1038/s41514-018-0029-z (opens in a new tab)PepBankPUB-30416740
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Summary

Cognitive dysfunction is one of the most concerning outcomes in global population aging. However, the mechanisms by which cognitive functions are impaired during aging remain elusive. It has been established that NAD+ levels are reduced in multiple tissues and organs, including the brain. We found that NAD+ levels declined in the hippocampus of mice during the course of aging, and whereas we observed minimal age-related effects on spatial learning/memory capabilities in old mice, we discovered that they developed cognitive hypersensitivity in response to aversive stimulation during contextual fear conditioning tests. This cognitive hypersensitivity appears to be associated with alterations in emotionality (fear/anxiety) and sensory processing (shock sensitivity), rather than reflect genuine conditioning/retention effects, during aging. Supplementation of nicotinamide mononucleotide (NMN) improved the sensory processing aspect of the hypersensitivity and possibly other related behaviors. Specific knockdown of nicotinamide phosphoribosyltransferase (Nampt) in the CA1 region, but not in the dentate gyrus, recapitulates this cognitive hypersensitivity observed in old mice. We identified calcium/calmodulin-dependent serine protein kinase (Cask) as a potential downstream effector in response to age-associated NAD+ reduction in the hippocampus. Cask expression is responsive to NAD+ changes and also reduced in the hippocampus during aging. Short-term NMN supplementation can enhance Cask expression in the hippocampus of old mice. Its promoter activity is regulated in a Sirt1-dependent manner. Taken together, NAD+ reduction in the CA1 region contributes to development of age-associated cognitive dysfunction, aspects of which may be prevented or treated by enhancing NAD+ availability through supplementation of NAD+ intermediates, such as NMN.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In old mice, NMN improved the sensory processing component of hypersensitivity to aversive stimulation.

    In plain wordsIn old mice, NMN reduced excessive sensitivity to unpleasant stimulation.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    DecreaseSensory processing hypersensitivity
    Study

    mousen: not reported in source

    Old mice
    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Supplementation of nicotinamide mononucleotide (NMN) improved the sensory processing aspect of the hypersensitivity and possibly other related behaviors.
    1 context sentence
    Summary · context
    This cognitive hypersensitivity appears to be associated with alterations in emotionality (fear/anxiety) and sensory processing (shock sensitivity), rather than reflect genuine conditioning/retention effects, during aging.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In old mice, short-term NMN supplementation can enhance hippocampal Cask expression.

    In plain wordsIn old mice, short-term NMN can increase Cask expression in the hippocampus.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    IncreaseHippocampal Cask expression
    Study

    mousen: not reported in source

    Old mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · Short-termAs given in this study (mouse).

    Source sentences

    Summary
    Short-term NMN supplementation can enhance Cask expression in the hippocampus of old mice.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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