Evidence map›Paper›PMID 42178562›Full record

ArticleJournal of neuroinflammation2026

Microglial Ccl4-Ccr5 signaling links systemic inflammation to synaptic loss and memory deficits in chronic kidney disease.

Yaochen Cao, Jingyun Wang, Xitong Li, Xin Chen, Jinsheng Xiong, Tianyao Wang, Hongming Sun, Ziqiang Wang

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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. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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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

8 authors.

Yaochen Cao *Department of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou, Hannan, 570102, China.
Jingyun Wang *Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Xitong Li *Department of Nephrology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, 10117, Germany.
Xin ChenDepartment of Nephrology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, 10117, Germany.
Jinsheng XiongFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Tianyao WangDepartment of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, Harbin, China.
Hongming SunDepartment of Neurology, Daping Hospital, Third Military Medical University, No. 30 Gaotanyanzheng Street, Shapingba District, Chongqing, 400042, China. pt6r8bnx@s.okayama-u.ac.jp.
Ziqiang WangDepartment of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou, Hannan, 570102, China. ziqiangwang1986@163.com.

Funding

Academic Enhancement Support Program of Hainan Medical University XSTS2025101National Natural Science Foundation of China No. 82360151
6 · The paper itself

Abstract

backgroundChronic kidney disease (CKD) is increasingly associated with cognitive impairment, yet the molecular pathways connecting systemic inflammation to synaptic dysfunction remain unclear. This study investigates the role of the Ccl4-Ccr5 axis in microglia-mediated synaptic phagocytosis during CKD-associated cognitive decline.

methodsA 5/6 nephrectomy rat model was established in rats to induce CKD, validated by renal function markers. Cognitive performance was evaluated through spatial, contextual, and recognition memory tests. Hippocampal cellular alterations were analyzed using single-cell RNA sequencing and immunofluorescence for microglial activation and synaptic density. The functional roles of Ccr5 were assessed via in vivo and in vitro CRISPR-mediated knockdown or overexpression, while Ccl4-Ccr5 interactions were confirmed by co-immunoprecipitation.

resultsCKD rats showed significant cognitive deficits, increased hippocampal microgliosis, and synaptic loss. Ccr5 knockdown reduced microglial synaptic engulfment, restored synaptic plasticity, and improved memory, whereas Ccr5 overexpression enhanced phagocytic activity.

conclusionsThese findings demonstrate that Ccl4-Ccr5 signaling drives pathological synaptic elimination by microglia, linking systemic inflammation to cognitive decline in CKD. Targeting this pathway may provide a therapeutic approach to preserve neuronal function.

Indexed as

InflammationMemory DisordersMicrogliaReceptors, CCR5Renal Insufficiency, ChronicSynapsesAnimalsHippocampusMaleRatsRats, Sprague-DawleySignal TransductionReceptors, CCR5Ccl4-Ccr5 axisChronic kidney diseaseCognitive impairmentMicrogliaNeuroinflammationSynaptic phagocytosis

Identifiers

PMID42178562
PMCPMC13377755

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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.