Evidence map›Paper›PMID 40885845›Full record

ArticleMolecular psychiatry2025

Effects of esketamine on electrophysiology and metabolic reprogramming in brain organoids: insights into antidepressant mechanisms.

Mengjie Li, Wen Duan, Xiaoyan Hao, Shuangjie Li, Chen Wang, Yuanyuan Liang, Zhengwei Hu, Dongrui Ma, Mengnan Guo, Chunyan Zuo and 12 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. 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

22 authors.

Mengjie Li *Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Wen Duan *Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Xiaoyan HaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Shuangjie LiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Chen WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Yuanyuan LiangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Zhengwei HuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Dongrui MaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Mengnan GuoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Chunyan ZuoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Zhiyun WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Yanmei FengDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Chenwei HaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Shasha QiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Yuemeng SunDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Mibo TangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Chengyuan MaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Kenji HashimotoChiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan.ORCID http://orcid.org/0000-0002-8892-0439
Yuming XuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.ORCID http://orcid.org/0000-0003-2689-9897
Junliang YuanDepartment of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, 100191, Beijing, China. junliangyuan@bjmu.edu.cn.
Jianjun YangDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. yjyangjj@zzu.edu.cn.
Changhe ShiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. shichanghe@zzu.edu.cn.ORCID http://orcid.org/0000-0001-8704-4871

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82171247National Natural Science Foundation of China (National Science Foundation of China) 82371433
6 · The paper itself

Abstract

Esketamine, commonly used to treat treatment-resistant depression, has pharmacological mechanisms that remain incompletely understood. Brain organoids offer a human-relevant platform for investigating the cellular and molecular effects of drugs. In this study, we investigated the effects of esketamine on the electrophysiology and metabolism of brain organoids derived from iPSCs of healthy control subjects and depressed patients. Continuous monitoring revealed that esketamine treatment significantly decreased both the frequency and amplitude of action potentials, with the most pronounced reduction occurring within 4 h. High concentrations (1.5 mg/L) produced a stronger inhibitory effect, while organoids treated with a low concentration (0.25 mg/L) showed a recovery in action potential frequency after one week, although levels remained below pre-treatment values-a recovery not observed in the high-concentration group. Single-cell RNA sequencing demonstrated that esketamine modulated energy metabolism and induced metabolic reprogramming in a concentration- and time-dependent manner. Furthermore, by inhibiting oxidative phosphorylation and glycolysis separately and assessing cytosolic Ca

Indexed as

Antidepressive AgentsBrainKetamineOrganoidsAction PotentialsAdultDepressive Disorder, Treatment-ResistantEnergy MetabolismFemaleGlycolysisHumansInduced Pluripotent Stem CellsMaleMetabolic ReprogrammingOxidative PhosphorylationReceptors, N-Methyl-D-AspartateAntidepressive AgentsEsketamineKetamineReceptors, N-Methyl-D-Aspartate

Identifiers

PMID40885845

What OpenQuestion holds

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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.