Evidence map›Paper›PMID 40075039›Full record

ArticleMolecular neurobiology2025

TREM2 Modulates Postoperative Cognitive Function in Aged Mice by Inhibiting the NLRP3/caspase-1 Pathway and Apoptosis via PLCγ2 Activation.

Xinyue Zhang, Renyi Wang, Xue Pan, Zitong Chen, Yilong Li, Yue Hu, Fang Liu, Xuezhao Cao

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Targeting neuroinflammation and PVNMaterials today. Bio · 2026
    Article
  2. Article
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.

Xinyue Zhang *Department of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Renyi Wang *Department of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Xue PanDepartment of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Zitong ChenDepartment of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Yilong LiDepartment of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Yue HuDepartment of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Fang LiuDepartment of Neurology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. liufang219@163.com.
Xuezhao CaoDepartment of Anesthesiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. xzcao@cmu.edu.cn.

Funding

National Natural Science Foundation of China 82471287
6 · The paper itself

Abstract

Postoperative cognitive dysfunction (POCD) is a prevalent complication in elderly patients, with neuroinflammation identified as a key contributing factor. This study investigates the therapeutic potential of the TREM2-PLCγ2 signaling pathway in mitigating neuroinflammation, neuronal apoptosis and cognitive impairment following surgery. We employed both in vivo and in vitro models to investigate the effects of TREM2 activation and its interaction with PLCγ2. Mice subjected to surgery were pre-treated with the TREM2-activating peptide COG1410, and subsequently evaluated for neuroinflammation, neuronal apoptosis, and cognitive function. In vitro studies using microglial cells were conducted to examine the mechanistic relationship between TREM2 and PLCγ2 phosphorylation via SYK. Knockdown experiments and SYK inhibition were performed to determine the hierarchical interaction between TREM2, PLCγ2, and their downstream influence on the NLRP3 inflammasome. Surgery significantly elevated the activation of the NLRP3 inflammasome, along with increased Cleaved Caspase-1, IL-1β, IL-18, and neuronal apoptosis markers. Pre-treatment with COG1410 effectively reduced these pro-inflammatory and pro-apoptotic markers, while alleviating cognitive impairment. TREM2 activation promoted SYK-dependent phosphorylation of PLCγ2, which inhibited NLRP3 inflammasome activation and reduced neuroinflammation. TREM2 knockdown exacerbated microglial inflammation, while PLCγ2 knockdown suppressed NLRP3 activation. Inhibition of SYK impaired the protective effects of the TREM2-PLCγ2 pathway and delayed cognitive recovery in mice. RNA-sequencing further revealed significant alterations in pathways related to neuroinflammation and apoptosis. TREM2 modulates PLCγ2 activity through SYK phosphorylation, thereby alleviating microglial-driven neuroinflammation and neuronal apoptosis, and improving cognitive impairment following surgery. Targeting the TREM2-PLCγ2 pathway presents a promising strategy for the prevention and treatment of POCD.

Indexed as

AgingApoptosisCaspase 1CognitionMembrane GlycoproteinsNLR Family, Pyrin Domain-Containing 3 ProteinPhospholipase C gammaPostoperative Cognitive ComplicationsReceptors, ImmunologicSignal TransductionAnimalsInflammasomesMaleMiceMice, Inbred C57BLMicrogliaCaspase 1InflammasomesMembrane GlycoproteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePhospholipase C gammaReceptors, ImmunologicSyk KinaseTrem2 protein, mouseApoptosisMicrogliaNeuroinflammationPLCγ2Postoperative cognitive dysfunctionTREM2

Identifiers

What Socratic 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 Socratic graph.