Evidence map›Paper›PMID 41578331›Full record

ArticleJournal of neuroinflammation2026

A microglial LCN2-MC4R signaling axis drives silica-induced neuronal damage via C1q release.

Xia Li, Zihao Xie, Hangbing Cao, Fei Wang, Ruiqing Yan, Jianxin Wang, Chao Liu, Jialing Wang, Min Mu, Yan Liu and 3 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

13 authors.

Xia Li *School of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
Zihao Xie *Joint Research Center for Occupational Medicine and Health of IHM, Anhui University of Science and Technology, Huainan, 232001, China.
Hangbing CaoSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
Fei WangSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232001, China.
Ruiqing YanSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
Jianxin WangSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232001, China.
Chao LiuSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232001, China.
Jialing WangAnhui University of Science and Technology First Affiliated Hospital, Huainan, 230026, China.
Min MuSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
Yan LiuSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
ShanShan LingSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China.
Huiyu YeSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China. yehuiyu11@163.com.
Xinrong TaoSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, 231131, China. xrtao1116@hotmail.com.

Funding

Anhui Provincial Special Program for Clinical and Translational Medical Research No.202304295107020033University Synergy Innovation Program of Anhui Province GXXT-2021-077
6 · The paper itself

Abstract

Silica exposure precipitates irreversible lung injury; however, its long-term neurological sequelae—and the microglial mechanisms underlying these effects—remain poorly understood. Here, we demonstrate that inhaled crystalline silica induces persistent hippocampal inflammation, anxiety- and depression-like behaviors, and neuronal loss in mice. Bulk RNA sequencing, immunophenotyping, and pharmacological depletion studies revealed that microglia are the primary source of complement C1q in silica-exposed brains. Mechanistically, silica-induced lipocalin-2 (LCN2) engages the melanocortin-4 receptor (MC4R) on microglia, activating a cAMP/PKA/NF-κB cascade that transcriptionally upregulates C1q. Pharmacological blockade of MC4R (using PF) abolished C1q overproduction, normalized brain-derived neurotrophic factor levels, and restored both synaptic integrity and behavioral performance. Our findings establish the LCN2–MC4R–C1q axis as a critical microglial pathway in silica-related neurotoxicity and identify MC4R antagonism as a promising, readily translatable intervention for occupational neuroinflammation.

Indexed as

Complement C1qLipocalin-2MicrogliaNeuronsReceptor, Melanocortin, Type 4Signal TransductionSilicon DioxideAnimalsMaleMiceMice, Inbred C57BLComplement C1qLcn2 protein, mouseLipocalin-2Receptor, Melanocortin, Type 4Silicon DioxideC1qLCN2Lung-brain axisMC4RMicrogliaNeuroinflammation

Identifiers

PMID41578331
PMCPMC12911259

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.