Evidence map›Paper›PMID 42243539›Full record

ArticleCommunications biology2026

NR3C1/PRKACG-mediated impairment of mitochondrial quality control underlies stress-induced hypothalamic neuronal injury.

Guowei Zhang, Jingze Cong, Xiaowei Feng, Hongjian Xin, Weihao Zhu, Rui Shi, Chenyu Li, Yang Wang, Rufei Ma, Yingmin Li and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

12 authors.

Guowei Zhang *Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Jingze Cong *Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Xiaowei FengHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Hongjian XinHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Weihao ZhuHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Rui ShiHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Chenyu LiHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Yang WangHuaihai Hospital Affiliated to Xuzhou Medical University, Xuzhou, China.
Rufei MaHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Yingmin LiHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.
Bin CongHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. cong6406@hebmu.edu.cn.ORCID 0000-0003-3349-7204
Weibo ShiHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. shiweibo@hebmu.edu.cn.ORCID 0000-0001-9601-3188

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The hypothalamus integrates autonomic, endocrine, and behavioral responses to stress, and stress-induced hypothalamic neuronal injury is implicated in various diseases. However, the underlying molecular mechanisms remain unclear. Mitochondria, as stress-sensitive organelles, play a critical role in cellular injury through structural and functional alterations. Here, we investigate how stress triggers mitochondrial quality control (MQC) dysfunction via glucocorticoid receptor (NR3C1) signaling, contributing to hypothalamic neuronal injury. Using acute and chronic stress rat models, we demonstrate that stress induces hypothalamic neuronal damage. Transmission electron microscopy and WB analysis reveal that stress promotes excessive mitochondrial fission while suppressing fusion, disrupting mitochondrial dynamics. At the cellular level, ChIP-Seq and siRNA experiments confirm that glucocorticoids (GCs) downregulate PRKACG (protein kinase A catalytic subunit gamma) expression via NR3C1-mediated transcriptional repression, reducing DRP1 (dynamin-related protein 1) phosphorylation at Ser637 and leading to aberrant mitochondrial fission. Furthermore, acute and chronic stress differentially activate mitophagy pathways, resulting in mitochondrial depletion. Intriguingly, neuronal death shifts from apoptosis to necroptosis under prolonged stress. In conclusion, our findings establish that NR3C1/PRKACG-mediated MQC dysfunction is a key mechanism in stress-induced hypothalamic neuronal injury. This study not only elucidates how GCs disrupt MQC but also advances our understanding of mitochondrial dysregulation in stress-related neuronal damage, providing a foundation for future mechanistic and therapeutic investigations.

Indexed as

CalcineurinHypothalamusMitochondriaNeuronsReceptors, GlucocorticoidStress, PhysiologicalAnimalsDynaminsMaleMitochondrial DynamicsRatsRats, Sprague-DawleySignal TransductionCalcineurinDnm1l protein, ratDynaminsReceptors, Glucocorticoid

Identifiers

PMID42243539
PMCPMC13554088

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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.