Evidence map›Paper›PMID 42461891›Full record

ArticleNeuroimmunomodulation2026

The Mechanism of Carboxypeptidase E Regulating NLRP3 Inflammasome Signaling in the Pathogenesis of Depression-Like Behaviors in Mice.

Xili Yang, Zhimin Qi, Song Huang, Xinyan Zhao, Yueyang You, Huiying Liu, Shuchun Yu, Xiaohong Du, Fan Xiao

Abstract read
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Article in Neuroimmunomodulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xili YangDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Zhimin QiDepartment of Anesthesiology, The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Song HuangDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Xinyan ZhaoDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Yueyang YouDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Huiying LiuThe Institute of Translational Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Shuchun YuDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Xiaohong DuDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China, duxiaohongg@outlook.com.
Fan XiaoDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China, xiaofanz0@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDepression is a common mental disease. Carboxypeptidase E (CPE) may be a therapeutic target for depression. This study aimed to investigate whether CPE regulates NOD-like receptor protein 3 (NLRP3) inflammasome signaling and affects pyroptosis, thereby improving cellular damage and depression-like behaviors in depressed mice.

methodsA mouse model of depression-like behavior was established with chronic unpredictable mild stress (CUMS) and treated with Lv-oe-CPE, an NLRP3 inflammasome activator (nigericin), or an NLRP3 inflammasome inhibitor (MCC950). Anxiety- and depression-like behaviors were assessed through open field test, forced swim test, tail suspension test, and sucrose preference test. Cellular damage in the hippocampal CA1 region was evaluated with H&E and Nissl staining. CPE, gasdermin D-N (GSDMD-N), NLRP3, cleaved caspase 1, apoptosis-associated spot-like protein (ASC), oxidative stress, interleukin (IL)-1β, and IL-18 levels, and GSDMD-N-positive cells were assessed with Western blot, kits, and immunohistochemistry.

resultsCPE was downregulated in the hippocampal CA1 region of CUMS mice, and its reexpression attenuate depression-like behaviors. CPE overexpression suppressed NLRP3, cleaved caspase 1, ASC, IL-1β, and IL-18 levels in the hippocampal CA1 region. NLRP3 inflammasome inactivation alleviated CA1 cellular damage to inhibit depressive-like behaviors, whereas its activation reversed the improving effect of CPE. CPE inactivated NLRP3 inflammasomes, thereby attenuating cell pyroptosis in the hippocampal CA1 region.

conclusionsCPE is downregulated in the hippocampal CA1 region of the mouse model of depression-like behavior. CPE overexpression can inhibit NLRP3 inflammasome activation and then reduce pyroptosis, hence repairing cellular damage in the hippocampal CA1 region and eventually suppressing depressive-like behaviors.

Indexed as

Carboxypeptidase HDepressionInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsBehavior, AnimalCA1 Region, HippocampalDisease Models, AnimalMaleMiceMice, Inbred C57BLPyroptosisSignal TransductionStress, PsychologicalCarboxypeptidase HInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseCarboxypeptidase ECellular damageDepression-like behaviorsGasdermin D-NHippocampal CA1 regionInflammasomeNOD-like receptor protein 3Pyroptosis

Identifiers

PMID42461891
PMCPMC13506152

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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.