Evidence map›Paper›PMID 39603853›Full record

ArticleBritish journal of anaesthesia2025

Structural basis for the inhibition of cystathionine-β-synthase by isoflurane and its role in anaesthesia-induced social dysfunction in mice.

Mengfan He, Hanxi Wan, Peilin Cong, Xinyang Li, Chun Cheng, Xinwei Huang, Qian Zhang, Huanghui Wu, Li Tian, Ke Xu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of anaesthesia, 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

11 authors.

Mengfan HeShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Hanxi WanShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Peilin CongShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Xinyang LiShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Chun ChengShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Xinwei HuangShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Qian ZhangShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Huanghui WuShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Li TianShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: ltian@tongji.edu.cn.
Ke XuShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: kx2129@tongji.edu.cn.
Lize XiongShanghai Key Laboratory of Anaesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Centre for Anaesthesiology and Perioperative Medicine, Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: mzkxlz@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAnaesthesia has been shown to impair social functioning, but the underlying mechanisms remain largely unknown. The volatile anaesthetic isoflurane potentially disrupts the methionine cycle and trans-sulphuration pathway, contributing to social deficits. Cystathionine-β-synthase (CBS), a key enzyme in this pathway, might be targeted by isoflurane. We investigated the CBS-isoflurane interaction and its role in neuronal function and social behaviour.

methodsMice aged 3-15 months were anaesthetised with 2 vol% isoflurane for 2 h, and social behaviours were tested 24 h after exposure. Alterations in neuronal activity were assessed using electrophysiological analysis in vivo. Pharmacological activators (S-adenosylmethionine [SAM]) or inhibitors (amino-oxyacetic acid [AOAA]), and adeno-associated virus (AAV) were used to modulate CBS activity. The binding site of isoflurane on CBS was determined using X-ray crystallography. A novel transgenic model with a point mutation knock-in was constructed to eliminate the CBS-isoflurane interaction.

resultsIsoflurane inhibited CBS activity (by 0.35-fold [0.07] vs 1.00-fold [0.05]; P<0.001), leading to neuronal hypoactivity in the anterior cingulate cortex (ACC) and social impairments in adult and elderly mice. SAM, AOAA, and AAV interventions demonstrated a causal link. Structural and functional analysis identified the lysine 273 (K273) in CBS to be involved in isoflurane inhibition. CBS K273A knock-in mice exhibited increased CBS activity compared with wild-type littermates after isoflurane exposure (2.2-fold [0.22] vs 1.0-fold [0.28]; P<0.001), with successful alleviation of ACC neuronal hypoactivity and social dysfunction.

conclusionsThese findings reveal a crucial role for CBS inhibition by isoflurane in anaesthesia-induced social impairment.

Indexed as

Anesthetics, InhalationCystathionine beta-SynthaseIsofluraneSocial BehaviorAnimalsBehavior, AnimalMaleMiceMice, Inbred C57BLMice, TransgenicAnesthetics, InhalationCystathionine beta-SynthaseIsofluranecrystallographycystathionine-β-synthaseisofluraneneuronal hypoactivitysocial behaviour

Identifiers

PMID39603853
PMCPMC11867083

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.