Evidence map›Paper›PMID 33472690›Full record

ArticleAlzheimer's research & therapy2021

Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer's disease-associated markers in 3xTg-AD mice.

Minesh Kapadia, M Firoz Mian, Donglai Ma, Craig P Hutton, Amber Azam, Klotilda Narkaj, Chuanhai Cao, Breanna Brown, Bernadeta Michalski, David Morgan and 4 more

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

Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
4.1field-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

6 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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

14 authors at 4 institutions in 2 countries.

Minesh KapadiaDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada.
M Firoz MianDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Donglai MaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Craig P HuttonDepartment of Psychology, Neuroscience, and Behaviour, McMaster University, Hamilton, ON, Canada.
Amber AzamDepartment of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
Klotilda NarkajDepartment of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
Chuanhai CaoDepartment of Pharmaceutical Science, University of South Florida, Tampa, FL, USA.
Breanna BrownDepartment of Pharmaceutical Science, University of South Florida, Tampa, FL, USA.
Bernadeta MichalskiDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada.
David MorganDepartment of Translational Science & Molecular Medicine, Michigan State University, Grand Rapids, MI, USA.
Paul ForsytheDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Iva B ZovkicDepartment of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
Margaret FahnestockDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada.
Boris SakicDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada. sakic@mcmaster.ca.ORCID 0000-0002-0531-4872
McMaster University · CAUniversity of Toronto · CAUniversity of South Florida · USMichigan State University · US

Funding

CIHR PJT-149031
6 · The paper itself

Abstract

backgroundCirculating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer's disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model.

methodsYoung 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration.

resultsChronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors.

conclusionThe results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalEpigenesis, GeneticFemaleImmunosuppression TherapyMaleMiceMice, Inbred C57BLMice, TransgenicPlaque, Amyloidtau ProteinsAmyloid beta-PeptidesAmyloid beta-Protein Precursortau Proteins3xTg-AD miceAlzheimer’s diseaseAmyloid-betaAutoantibodiesAutoimmunityBDNFCyclophosphamideHistone variantsSexTauT lymphocytes

Identifiers

PMID33472690
PMCPMC7818784
OpenAlexW3118711961

What OpenQuestion 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 OpenQuestion graph.