Evidence map›Paper›PMID 32599538›Full record

ArticleJournal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)2020

Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer's disease.

Siok Lam Lim, Carlos J Rodriguez-Ortiz, Heng-Wei Hsu, Jie Wu, Joannee Zumkehr, Jason Kilian, Janielle Vidal, Pinar Ayata, Masashi Kitazawa

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

Article in Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Are high copper levels related to Alzheimer's and Parkinson's diseases? A systematic review and meta-analysis of articles published between 2011 and 2022.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024
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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

9 authors at 2 institutions in 1 country.

Siok Lam LimCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Carlos J Rodriguez-OrtizCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Heng-Wei HsuCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Jie WuDepartment of Biological Chemistry, University of California, Irvine, CA, USA.
Joannee ZumkehrCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Jason KilianCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Janielle VidalCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
Pinar AyataNash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, NY, USA.
Masashi KitazawaCenter for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA. Electronic address: kitazawa@uci.edu.
University of California, Irvine · USIcahn School of Medicine at Mount Sinai · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Understanding the mechanism of SPl1 dependent Alzheimer disease riskRF1AG054011 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GOATE, ALISON M · 2016 to 2016
$4.2M
Environmental copper exposure and its impact on microglial Abeta clearanceR01ES024331 · NIEHS · UNIVERSITY OF CALIFORNIA, MERCED · PI KITAZAWA, MASASHI · 2014 to 2018
$2.7M
PacBio RS Single Molecule, Real-Time (SMRT) DNA SequencerS10OD010794 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2012 to 2012
$600k
High-Throughput DNA SequencerS10OD021718 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2016 to 2016
$600k
High Throughput DNA SequencerS10RR025496 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2009 to 2009
$500k
NCI NIH HHS P30 CA062203NCRR NIH HHS S10 RR025496NIA NIH HHS RF1 AG054011NIEHS NIH HHS R01 ES024331NIH HHS S10 OD010794NIH HHS S10 OD021718
6 · The paper itself

Abstract

backgroundCopper (Cu) is an essential metal mediating a variety of vital biological reactions with its redox property. Its dyshomeostasis has been associated with accelerated cognitive decline and neurodegenerative disorders, such as Alzheimer's disease (AD). However, underlying neurotoxic mechanisms elicited by dysregulated Cu remain largely elusive. We and others previously demonstrated that exposure to Cu in drinking water significantly exacerbated pathological hallmarks of AD and pro-inflammatory activation of microglia, coupled with impaired phagocytic capacity, in mouse models of AD.

methodsIn the present study, we extended our investigation to evaluate whether chronic Cu exposure to wild-type (WT) and J20 mouse model of AD perturbs homeostatic dynamics of microglia and contributes to accelerated transformation of microglia towards degenerative phenotypes that are closely associated with neurodegeneration. We further looked for evidence of alterations in the microglial morphology and spatial memory of the Cu-exposed mice to assess the extent of the Cu toxicity.

resultsWe find that chronic Cu exposure to pre-pathological J20 mice upregulates the translation of degenerative genes and represses homeostatic genes within microglia even in the absence amyloid-beta plaques. We also observe similar expression signatures in Cu-exposed WT mice, suggesting that excess Cu exposure alone could lead to perturbed microglial homeostatic phenotypes and contribute to accelerated cognitive decline.

conclusionOur findings highlight the risk of chronic Cu exposure on cognitive decline and altered microglia activation towards degenerative phenotypes. These changes may represent one of the key mechanisms linking Cu exposure or its dyshomeostasis to an increased risk for AD.

Indexed as

Alzheimer DiseaseAnimalsCognition DisordersCopperDisease Models, AnimalFemaleGene Expression RegulationInflammationMaleMice, Inbred C57BLMice, TransgenicMicrogliaTamoxifenToxicity Tests, ChronicCopperTamoxifenAlzheimer’s diseaseCopperMicrogliaTranslating ribosome affinity purification (TRAP)Translatome

Identifiers

PMID32599538
PMCPMC7655674
OpenAlexW3035899184

What OpenQuestion holds

Textmetadata
LicenceTDM
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.