Evidence map›Paper›PMID 36804009›Full record

ArticleJournal of neuroinflammation2023

Integrin Mac1 mediates paraquat and maneb-induced learning and memory impairments in mice through NADPH oxidase-NLRP3 inflammasome axis-dependent microglial activation.

Liyan Hou, Jianing Liu, Fuqiang Sun, Ruixue Huang, Rui Chang, Zhengzheng Ruan, Ying Wang, Jie Zhao, Qingshan Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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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.

Liyan Hou *Dalian Medical University Library, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Jianing Liu *School of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Fuqiang SunSchool of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Ruixue HuangSchool of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Rui ChangSchool of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Zhengzheng RuanSchool of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Ying WangSchool of Public Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Jie ZhaoNational-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, 116044, China. zhaoj@dmu.edu.cn.
Qingshan WangNational-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, 116044, China. wangq4@126.com.

Funding

Liaoning Provincial Natural Science Foundation of China 2020-MS-264
6 · The paper itself

Abstract

introductionThe mechanisms of cognitive impairments in Parkinson's disease (PD) remain unknown. Accumulating evidence revealed that brain neuroinflammatory response mediated by microglial cells contributes to cognitive deficits in neuropathological conditions and macrophage antigen complex-1 (Mac1) is a key factor in controlling microglial activation.

objectivesTo explore whether Mac1-mediated microglial activation participates in cognitive dysfunction in PD using paraquat and maneb-generated mouse PD model.

methodsCognitive performance was measured in wild type and Mac1

resultsGenetic deletion of Mac1 significantly ameliorated learning and memory impairments, neuronal damage, synaptic loss and α-synuclein phosphorylation (Ser129) caused by paraquat and maneb in mice. Subsequently, blocking Mac1 activation was found to mitigate paraquat and maneb-elicited microglial NLRP3 inflammasome activation in both in vivo and in vitro. Interestingly, stimulating activation of NOX by phorbol myristate acetate abolished the inhibitory effects of Mac1 blocking peptide RGD on paraquat and maneb-provoked NLRP3 inflammasome activation, indicating a key role of NOX in Mac1-mediated NLRP3 inflammasome activation. Furthermore, NOX1 and NOX2, two members of NOX family, and downstream PAK1 and MAPK pathways were recognized to be essential for NOX to regulate NLRP3 inflammasome activation. Finally, a NLRP3 inflammasome inhibitor glybenclamide abrogated microglial M1 activation, neurodegeneration and phosphorylation (Ser129) of α-synuclein elicited by paraquat and maneb, which were accompanied by improved cognitive capacity in mice.

conclusionsMac1 was involved in cognitive dysfunction in a mouse PD model through NOX-NLRP3 inflammasome axis-dependent microglial activation, providing a novel mechanistic basis of cognitive decline in PD.

Indexed as

ManebParaquatParkinson Diseasealpha-SynucleinAnimalsDisease Models, AnimalDopaminergic NeuronsInflammasomesIntegrinsMacrophage-1 AntigenMacrophagesMemory DisordersMiceMicrogliaNADPH OxidasesNLR Family, Pyrin Domain-Containing 3 Proteinalpha-SynucleinInflammasomesIntegrinsMacrophage-1 AntigenManebNADPH OxidasesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseParaquatIntegrinLearning and memory deficitsMicroglial activationNADPH oxidaseNLRP3 inflammasomeParkinson’s diseasePesticide

Identifiers

PMID36804009
PMCPMC9938991

What OpenQuestion 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 OpenQuestion graph.