Evidence map›Paper›PMID 41559779›Full record

ArticleJournal of neuroinflammation2026

Compromised hepatic bilirubin clearance drives depressive symptoms via regulating microglial engulfment of dendritic spines.

Shuaijie Sun, Mengyu Li, Jun Ma, Keqiang He, Li Wang, Chunliu Li, Xiangru Liu, Shiyuan Zhang, Tianyue Yin, Mengmeng Yang and 6 more

Abstract read
PubMed Full text at PMC Publisher
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.

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

16 authors.

Shuaijie Sun *Department of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Mengyu Li *Department of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Jun Ma *Department of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Keqiang He *Department of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Li WangDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Chunliu LiDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Xiangru LiuDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Shiyuan ZhangDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Tianyue YinDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Mengmeng YangDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Xinlu YangDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Jiaming ZhangHefei National Research Center for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
Chengjun XuDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Zhong LiHefei National Research Center for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. zhongcli@ustc.edu.cn.
Sheng WangDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China. iamsheng2020@ustc.edu.cn.
Hongrui ZhuDepartment of Pain and Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China. zhuhongrui@mail.ustc.edu.cn.ORCID http://orcid.org/0000-0001-6823-6827

Funding

The National Natural Science Foundation of China 82272225USTC Research Funds of the Double First-Class Initiative YD9110002084
6 · The paper itself

Abstract

backgroundMajor depressive disorder (MDD) remains a debilitating global health issue with limited treatment efficacy. Liver qi stagnation (or called liver depression) has been associated with MDD, but the underlying mechanisms are poorly understood. This study investigates whether impaired hepatic function contributes to depressive symptomatology.

methodsUsing retrospective clinical data, chronic unpredictable stress (CUMS) models, orthotopic liver transplantation, and microglia-specific genetic tools (including TRPM2 and SYK conditional knockouts), we combined behavioral assays, multi-omics, electrophysiology, and optogenetics to explore the liver-brain axis in depression.

resultsCompromised hepatic bilirubin clearance in depressive subjects drives depressive symptoms by enhancing microglial engulfment of dendritic spines in the anterior cingulate cortex (ACC). Clinical evidence highly reveals a correlation between hyperbilirubinemia and MDD severity, mirrored in chronic stress mouse models. Liver transplantation from stressed to non-stressed mice impaired bilirubin clearance and induced depressive behaviors, accompanied by ACC glutamatergic neuronal hypoactivity (ACC

conclusionOur results reveal a novel liver-brain pathway whereby impaired bilirubin clearance drives depression via microglial synaptic pruning. Targeting microglial TRPM2 offers a promising therapeutic strategy for MDD.

Indexed as

BilirubinDendritic SpinesDepressionLiverMicrogliaAnimalsGyrus CinguliHumansLiver TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutStress, PsychologicalBilirubinBilirubinDepressionLiver-brain axisMicrogliaNeuroinflammationPause-releaseTRPM2

Identifiers

PMID41559779
PMCPMC12829269

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.