Evidence map›Paper›PMID 38904658›Full record

ArticleeLife2024

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Elissavet Chartampila, Karim S Elayouby, Paige Leary, John J LaFrancois, David Alcantara-Gonzalez, Swati Jain, Kasey Gerencer, Justin J Botterill, Stephen D Ginsberg, Helen E Scharfman

Abstract read
In one paragraph

Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Neuro-Adipokine Crosstalk in Alzheimer's Disease.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Effect of choline supplementation in presymptomaticAlzheimer's & dementia (New York, N. Y.)
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Elissavet ChartampilaCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Karim S ElayoubyCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Paige LearyCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.ORCID https://orcid.org/0000-0002-0888-466X
John J LaFrancoisCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
David Alcantara-GonzalezCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Swati JainCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Kasey GerencerCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Justin J BotterillCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Stephen D GinsbergCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.
Helen E ScharfmanCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, United States.ORCID https://orcid.org/0000-0003-4006-3383

Funding

Hyperexcitability in Alzheimer's DiseaseR01AG055328 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI SCHARFMAN, HELEN E · 2017 to 2021
$2.0M
Hyperexcitability in Alzheimer's DiseaseRF1AG055328 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI Helen E Scharfman · 2024 to 2026
$2.0M
Mossy Cells in Temporal Lobe EpilepsyR37NS126529 · NINDS · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI Helen E Scharfman · 2023 to 2026
$1.9M
Alzheimer's Association AARFD-22-926807Natural Sciences and Engineering Research Council of Canada RGPIN-2023-03400New York State Office of Mental Health no numberNIA NIH HHS R01 AG055328NIA NIH HHS RF1 AG055328NIH HHS AG 055328NINDS NIH HHS R37 NS126529
6 · The paper itself

Abstract

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.

Indexed as

Alzheimer DiseaseCholineDietary SupplementsDisease Models, AnimalAnimalsDentate GyrusDNA-Binding ProteinsFemaleMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsProto-Oncogene Proteins c-fosCholineDNA-Binding ProteinsFosb protein, mouseNerve Tissue ProteinsNeuN protein, mouseProto-Oncogene Proteins c-fosAlzheimer's diseasedentate gyrusdietexcitabilityhyperactivitymemorymouseneuroscience

Identifiers

PMID38904658
PMCPMC11192536

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.