Evidence map›Paper›PMID 35397630›Full record

ArticleCell death & disease2022

Simvastatin rescues memory and granule cell maturation through the Wnt/β-catenin signaling pathway in a mouse model of Alzheimer's disease.

Xin-Kang Tong, Jessika Royea, Edith Hamel

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Unraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
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  11. Review
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  14. Review
  15. Article
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  18. Review
  19. Article
  20. Inhibition of VDAC1 Rescues AMediators of inflammation · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Xin-Kang TongLaboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, 3801 University Street, H3A 2B4, Montréal, QC, Canada.
Jessika RoyeaLaboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, 3801 University Street, H3A 2B4, Montréal, QC, Canada.ORCID 0000-0001-8790-3912
Edith HamelLaboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, 3801 University Street, H3A 2B4, Montréal, QC, Canada. edith.hamel@mcgill.ca.ORCID 0000-0001-5223-7315
Montreal Neurological Institute and Hospital · CA

Funding

CIHR MOP-126001
6 · The paper itself

Abstract

We previously showed that simvastatin (SV) restored memory in a mouse model of Alzheimer disease (AD) concomitantly with normalization in protein levels of memory-related immediate early genes in hippocampal CA1 neurons. Here, we investigated age-related changes in the hippocampal memory pathway, and whether the beneficial effects of SV could be related to enhanced neurogenesis and signaling in the Wnt/β-catenin pathway. APP mice and wild-type (WT) littermate controls showed comparable number of proliferating (Ki67-positive nuclei) and immature (doublecortin (DCX)-positive) granule cells in the dentate gyrus until 3 months of age. At 4 months, Ki67 or DCX positive cells decreased sharply and remained less numerous until the endpoint (6 months) in both SV-treated and untreated APP mice. In 6 month-old APP mice, dendritic extensions of DCX immature neurons in the molecular layer were shorter, a deficit fully normalized by SV. Similarly, whereas mature granule cells (calbindin-immunopositive) were decreased in APP mice and not restored by SV, their dendritic arborizations were normalized to control levels by SV treatment. SV increased Prox1 protein levels (↑67.7%, p < 0.01), a Wnt/β-catenin signaling target, while significantly decreasing (↓61.2%, p < 0.05) the upregulated levels of the β-catenin-dependent Wnt pathway inhibitor DKK1 seen in APP mice. In APP mice, SV benefits were recapitulated by treatment with the Wnt/β-catenin specific agonist WAY-262611, whereas they were fully abolished in mice that received the Wnt/β-catenin pathway inhibitor XAV939 during the last month of SV treatment. Our results indicate that activation of the Wnt-β-catenin pathway through downregulation of DKK1 underlies SV neuronal and cognitive benefits.

Indexed as

Alzheimer DiseaseWnt Signaling PathwayAnimalsbeta CateninDisease Models, AnimalHippocampusKi-67 AntigenMiceNeurogenesisNeuronsSimvastatinbeta CateninKi-67 AntigenSimvastatin

Identifiers

PMID35397630
PMCPMC8994768
OpenAlexW4223429273

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.