Evidence mapPaperPMID 39334471Full record

ArticleJournal of neuroinflammation2024

Knockdown of microglial iron import gene, Slc11a2, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer's disease.

Katrina Volk Robertson, Alec S Rodriguez, Jean-Philippe Cartailler, Shristi Shrestha, Michael W Schleh, Kyle R Schroeder, Arianna M Valenti, Alec T Kramer, Fiona E Harrison, Alyssa H Hasty

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
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

2 citing papers in PubMed.

  1. Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026
    Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Katrina Volk RobertsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA.
Alec S RodriguezDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA.
Jean-Philippe CartaillerCreative Data Solutions, Vanderbilt Center for Stem Cell Biology, Nashville, TN, USA.
Shristi ShresthaCreative Data Solutions, Vanderbilt Center for Stem Cell Biology, Nashville, TN, USA.
Michael W SchlehDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA.
Kyle R SchroederDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA.
Arianna M ValentiDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA.
Alec T KramerVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Fiona E HarrisonDepartment of Medicine, Vanderbilt University Medical Center, 7465 Medical Research Building IV, 2213 Garland Avenue, Nashville, TN, 37232, USA. fiona.harrison@vumc.org.
Alyssa H HastyDepartment of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, TN, USA. alyssa.hasty@vanderbilt.edu.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1995 to 2025
$32.7M
MULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGYT32DK007563 · VANDERBILT UNIVERSITY · 1988 to 2025
$4.0M
SHOPP30EY008126 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1989 to 2025
$4.0M
TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · VANDERBILT UNIVERSITY · 1985 to 2025
$3.6M
Manganese exposure susceptibility as a modifier of excitotoxicity in Alzheimer's DiseaseR01ES031401 · NIEHS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Aaron B Bowman, Fiona Edith Harrison · 2022 to 2024
$1.6M
Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$1.2M
Vanderbilt Interdisciplinary Training Program in Alzheimer's DiseaseT32AG058524 · VANDERBILT UNIVERSITY · 2025 to 2025
$542k
BLRD VA IK6 BX005649NCI NIH HHS P30 CA068485NCRR NIH HHS G20 RR030956NCRR NIH HHS UL1 RR024975NEI NIH HHS P30 EY008126NIA NIH HHS AG058524NIA NIH HHS AG068082NIA NIH HHS P20 AG068082NIA NIH HHS T32 AG058524NICHD NIH HHS P50 HD103537NIDDK NIH HHS DK007563NIDDK NIH HHS DK121520-02S1NIDDK NIH HHS R01 DK121520NIDDK NIH HHS T32 DK007563NIEHS NIH HHS R01 ES031401NIEHS NIH HHS R01ES031401NIEHS NIH HHS T32 ES007028NIEHS NIH HHS T32ES007028
6 · The paper itself

Abstract

backgroundMicroglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer's disease (AD). In vitro, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo. These studies determined the effects of microglial-specific knockdown of Slc11a2 on AD-related cognitive decline and microglial transcriptional phenotype.

methodsIn vitro experiments and RT-qPCR were used to assess a role for DMT1 in amyloid-β-associated inflammation. To determine the effects of microglial Slc11a2 knockdown on AD-related phenotypes in vivo, triple-transgenic Cx3cr1

resultsDMT1 inhibition in vitro robustly decreased Aβ-induced inflammatory gene expression and cellular iron levels in conditions of excess iron. In vivo, Slc11a2

conclusionsThis work suggests a sex-specific role for microglial iron import gene Slc11a2 in propagating behavioral and cognitive phenotypes in the APP/PS1 model of AD. These data also highlight an association between loss of a DAM-like phenotype in microglia and cognitive deficits in Slc11a2

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorCation Transport ProteinsMice, TransgenicMicrogliaPresenilin-1Sex CharacteristicsAnimalsCognitionDisease Models, AnimalFemaleGene Knockdown TechniquesIronMaleMiceMice, Inbred C57BLAmyloid beta-Protein PrecursorCation Transport ProteinsIronPresenilin-1Solute Carrier Family 11, Member 2Alzheimer’s diseaseAPP/PS1BehaviorDMT1InflammationIronMicrogliaNeuroinflammationSex differencesSlc11a2

Identifiers

PMID39334471
PMCPMC11438269

What Socratic holds

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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 Socratic graph.