Evidence map›Paper›PMID 42278596›Full record

ArticleInternational journal of molecular sciences2026

Adenosine A2A Receptor Contributes to Bidirectional Remodeling of Microglial Inflammatory Responses During Methamphetamine Exposure.

Zhenping Hou, Xinjie Zhang, Genmeng Yang, Baoyu Shen, Wenjuan Dong, Di Jing, Shijun Hong, Lihua Li

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Zhenping HouNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Xinjie ZhangNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Genmeng YangNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Baoyu ShenNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Wenjuan DongNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Di JingNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.
Shijun HongNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.ORCID 0000-0002-3186-734X
Lihua LiNational Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, China.

Funding

National Natural Science Foundation of China 82260336, 82371898Scientific Research Fund of the Yunnan Provincial Department of Education 2023Y0781
6 · The paper itself

Abstract

To investigate the role of the adenosine A2A receptor (A2AR) in methamphetamine (MA)-induced microglia-mediated neuroinflammation and to explore the potential signaling mechanism, postmortem human striatal tissue from MA users, a male C57BL/6 mouse model of MA exposure, and the human microglial cell line HMC3 were examined by Western blotting, immunofluorescence, and related assays. Across all three experimental systems, MA exposure significantly upregulated A2AR expression together with alterations in downstream PKA and PKC signaling. These signaling changes were accompanied by parallel upregulation of pro-inflammatory mediators (iNOS, IL-1β, and IL-18) and of anti-inflammatory and repair-associated factors (Arg-1 and IL-10), suggesting that MA did not trigger a simple unidirectional inflammatory program but instead induced multidimensional phenotypic remodeling of microglia that varied with exposure time and dose. Intervention with the selective A2AR antagonist SCH58261 showed that pharmacological inhibition of A2AR markedly attenuated MA-induced alterations in PKA/PKC signaling and suppressed the accompanying shifts in inflammatory mediator expression, thereby mitigating the neuroinflammatory response. These results suggest that A2AR is involved in the modulation of MA-induced microglial inflammatory responses and may contribute to the mixed inflammatory state characterized by simultaneous changes in pro-inflammatory and anti-inflammatory markers, possibly associated with PKA/PKC signaling. This study expands current understanding of the inflammatory basis of MA-related neurotoxicity and suggests A2AR as a potential target for therapeutic intervention in MA abuse.

Indexed as

InflammationMethamphetamineMicrogliaNeuroinflammatory DiseasesReceptor, Adenosine A2AAdenosine A2 Receptor AntagonistsAnimalsCell LineCyclic AMP-Dependent Protein KinasesHumansMaleMiceMice, Inbred C57BLProtein Kinase CSignal TransductionAdenosine A2 Receptor AntagonistsCyclic AMP-Dependent Protein KinasesMethamphetamineProtein Kinase CReceptor, Adenosine A2Aadenosine A2A receptormethamphetaminemicroglianeuroinflammationPKA/PKC signaling pathway

Identifiers

PMID42278596
PMCPMC13257104

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.