Evidence map›Paper›PMID 30923833›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2019

Copper-Induced Upregulation of MicroRNAs Directs the Suppression of Endothelial LRP1 in Alzheimer's Disease Model.

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

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

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
2.3field-weighted citation impact, top 13% 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, 2 syntheses or guidelines pooled it, 33 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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  17. Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer's disease.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2020
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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

7 authors at 1 institution in 1 country.

Heng-Wei HsuCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Carlos J Rodriguez-OrtizCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Siok Lam LimCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Joannee ZumkehrCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Jason G KilianCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Janielle VidalCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
Masashi KitazawaCenter for Occupational and Environmental Health (COEH), Department of Medicine, University of California, Irvine, California 92617-1830.
University of California, Irvine · US

Funding

Environmental copper exposure and its impact on microglial Abeta clearanceR01ES024331 · NIEHS · UNIVERSITY OF CALIFORNIA, MERCED · PI KITAZAWA, MASASHI · 2014 to 2018
$2.7M
NIEHS NIH HHS R01 ES024331
6 · The paper itself

Abstract

Chronic exposure to copper and its dyshomeostasis have been linked to accelerated cognitive decline and potentially increasing risk for Alzheimer's disease (AD). We and others have previously demonstrated that exposure to copper through drinking water significantly increased parenchymal amyloid-beta (Aβ) plaques and decreased endothelial low-density lipoprotein receptor-related protein 1 (LRP1) in mouse models of AD. In this study, we determined the underlying mechanisms that microRNA critically mediated the copper-induced loss of endothelial LRP1. In human primary microvascular endothelial cells (MVECs), microRNA-200b-3p, -200c-3p, and -205-5p were significantly elevated within the 24-h exposure to copper and returned to baseline after 48-h postexposure, which corresponded with the temporal change of LRP1 expression in these cells. Transient expression of synthetic microRNA-200b-3p, -200c-3p, or -205-5p on MVECs significantly decreased endothelial LRP1, and cotreatment of synthetic antagomirs effectively prevented the loss of LRP1 during copper exposure, collectively supporting the key regulatory role of these microRNAs in copper-induced loss of LRP1. In mice, a significant reduction of LRP1 in cortical vasculature was evident following 9 months exposure to 1.3 ppm copper in drinking water, although the levels of cortical microRNA-205-5p, -200b-3p, and -200c-3p were only marginally elevated. This, however, correlated with increased vascular accumulation of Aβ and impairment of spatial memory, indicating that copper exposure has the pivotal role in the vascular damage and development of cognitive decline.

Indexed as

Alzheimer DiseaseAnimalsBrainCell SurvivalCopperDisease Models, AnimalEndothelial CellsFemaleHumansLow Density Lipoprotein Receptor-Related Protein-1MaleMaze LearningMiceMice, Inbred C57BLMice, TransgenicMicroRNAsCoppercupric chlorideLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanMicroRNAsamyloid-betacognitionJ20 micemouse modelvasculature

Identifiers

PMID30923833
PMCPMC6592190
OpenAlexW2926530952

What OpenQuestion holds

Textmetadata
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.