Evidence map›Paper›PMID 40244426›Full record

ArticleMetabolic brain disease2025

High urea promotes mitochondrial fission and functional impairments in astrocytes inducing anxiety-like behavior in chronic kidney disease mice.

Xi Zhao, Shengyao Zhang, Mengna Wu, Binyun Zhang, Guoran Wan, Meng Zhang, Jing Li, Zhuo Fei, Guoqi Zhu, Shaoqiu Jiang and 5 more

Abstract read
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Article in Metabolic brain disease, 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. Article
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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

15 authors.

Xi Zhao *Department of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Shengyao Zhang *Department of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Mengna WuDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Binyun ZhangDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Guoran WanDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Meng ZhangDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Jing LiDepartment of Stem Cell and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Zhuo FeiDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Guoqi ZhuDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Shaoqiu JiangDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Mohan XiaoDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Wanjia LiuDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Zhelun ZhaoDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China.
Boyue HuangDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China. boyue960521@cqmu.edu.cn.ORCID 0000-0002-8065-3217
Jianhua RanDepartment of Anatomy, Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, 400016, China. ranjianhua@cqmu.edu.cn.ORCID 0000-0001-9676-570X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High urea can induce depression and anxiety. Activation of astrocytes is closely associated with psychiatric disorders. However, the pathological mechanism of whether high urea affects astrocyte structure and function to induce anxiety-like behaviors remain unclear. We established a high-urea chronic kidney disease (CKD) mouse model and found that these mice exhibited elevated levels of anxiety through behavioral experiments. Immunofluorescence and transmission electron microscopy studies of astrocytes revealed a decrease in density and branching of mPFC astrocytes. Additionally, we observed a significant reduction in ATP and BDNF levels in the mPFC and primary astrocytes of CKD mice induced by high urea. Analysis of gene expression differences in astrocytes between WT and high-urea mice indicated alterations in mitochondrial dynamics-related signaling pathways in astrocytes. We established a high-urea primary astrocyte model to assess mitochondrial function and levels of fusion and fission proteins. Treatment of primary astrocytes with high urea led to mitochondrial fragmentation and downregulation of Mfn2 expression. These results suggested that high urea downregulates Mfn2 expression in mPFC astrocytes, induced mitochondrial fusion-fission abnormalities, disrupted astrocyte energy metabolism, and promoted high-urea-related anxiety. Mfn2 may represent a potential therapeutic target for high-urea-related anxiety.

Indexed as

AnxietyAstrocytesMitochondrial DynamicsRenal Insufficiency, ChronicUreaAnimalsCells, CulturedDisease Models, AnimalMaleMiceMice, Inbred C57BLMitochondriaUreaAnxietyAstrocytesMitochondriaUrea

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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.