Evidence map›Paper›PMID 28476157›Full record

ArticleJournal of neuroinflammation2017

Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity.

Kelly S Kirkley, Katriana A Popichak, Maryam F Afzali, Marie E Legare, Ronald B Tjalkens

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 3 pooled it
12.9field-weighted citation impact, top 1% 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

190 citing papers in PubMed, 3 syntheses or guidelines pooled it, 313 citations in OpenAlex.

  1. Pooled it
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  12. Experimental neurobiology · 2026
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  13. Unravelling the novel insights between miR-7 and Parkinson's disease (PD).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
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130 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Kelly S KirkleyDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO, 80523-1680, USA.
Katriana A PopichakDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO, 80523-1680, USA.
Maryam F AfzaliDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO, 80523-1680, USA.
Marie E LegareDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO, 80523-1680, USA.
Ronald B TjalkensDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO, 80523-1680, USA. Ron.Tjalkens@colostate.edu.
Colorado State University · US

Funding

Neuroinflammation and developmental vulnerability to manganese toxicityR01ES021656 · NIEHS · COLORADO STATE UNIVERSITY · PI TJALKENS, RONALD · 2013 to 2022
$4.2M
NIEHS NIH HHS R01 ES021656
6 · The paper itself

Abstract

backgroundAs the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses. In diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and human immunodeficiency virus-induced dementia, activation of microglia precedes astrogliosis and overt neuronal loss. Although microgliosis is implicated in manganese (Mn) neurotoxicity, the role of microglia and glial crosstalk in Mn-induced neurodegeneration is poorly understood.

methodsExperiments utilized immunopurified murine microglia and astrocytes using column-free magnetic separation. The effect of Mn on microglia was investigated using gene expression analysis, Mn uptake measurements, protein production, and changes in morphology. Additionally, gene expression analysis was used to determine the effect Mn-treated microglia had on inflammatory responses in Mn-exposed astrocytes.

resultsImmunofluorescence and flow cytometric analysis of immunopurified microglia and astrocytes indicated cultures were 97 and 90% pure, respectively. Mn treatment in microglia resulted in a dose-dependent increase in pro-inflammatory gene expression, transition to a mixed M1/M2 phenotype, and a de-ramified morphology. Conditioned media from Mn-exposed microglia (MCM) dramatically enhanced expression of mRNA for Tnf, Il-1β, Il-6, Ccl2, and Ccl5 in astrocytes, as did exposure to Mn in the presence of co-cultured microglia. MCM had increased levels of cytokines and chemokines including IL-6, TNF, CCL2, and CCL5. Pharmacological inhibition of NF-κB in microglia using Bay 11-7082 completely blocked microglial-induced astrocyte activation, whereas siRNA knockdown of Tnf in primary microglia only partially inhibited neuroinflammatory responses in astrocytes.

conclusionsThese results provide evidence that NF-κB signaling in microglia plays an essential role in inflammatory responses in Mn toxicity by regulating cytokines and chemokines that amplify the activation of astrocytes.

Indexed as

AnimalsAstrocytesCells, CulturedCoculture TechniquesInflammation MediatorsManganeseMiceMice, Inbred C57BLMice, TransgenicMicrogliaInflammation MediatorsManganeseGlial crosstalkManganismNeuroinflammationNF-κBTumor necrosis factor

Identifiers

PMID28476157
PMCPMC5418760
OpenAlexW2611861607

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.