Evidence map›Paper›PMID 33526073›Full record

ArticleJournal of neuroinflammation2021

Fluoxetine regulates eEF2 activity (phosphorylation) via HDAC1 inhibitory mechanism in an LPS-induced mouse model of depression.

Weifen Li, Tahir Ali, Chengyou Zheng, Zizhen Liu, Kaiwu He, Fawad Ali Shah, Qingguo Ren, Shafiq Ur Rahman, Ningning Li, Zhi-Jian Yu and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
5.0field-weighted citation impact, top 3% of its field
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

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.

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  20. Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 3 countries.

Weifen LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Tahir AliState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Chengyou ZhengState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Zizhen LiuState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Kaiwu HeState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Fawad Ali ShahState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Qingguo RenDepartment of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
Shafiq Ur RahmanState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Ningning LiTomas Lindahl Nobel Laureate Laboratory, Precision Medicine Research Centre, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
Zhi-Jian YuDepartment of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, The 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. yuzhijiansmu@163.com.
Shupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. lisp@pku.edu.cn.ORCID http://orcid.org/0000-0002-7807-374X
Peking University · CNCentre for Addiction and Mental Health · CARiphah International University · PKShaheed Benazir Bhutto University · PKShenzhen University Health Science Center · CNSun Yat-sen University · CNZhongda Hospital Southeast University · CN

Funding

Collaborative Innovation Center for Water Treatment Technology and Materials (CN) JCYJ20170810163329510Sanming Project of Medicine in Shenzhen SZSM201911003Shenzhen-Hong Kong Institute of Brain Science 2019SHIBS0004Shenzhen Key Medical Discipline Construction Fund SZXK06162
6 · The paper itself

Abstract

backgroundSelective serotonin reuptaker inhibitors, including fluoxetine, are widely studied and prescribed antidepressants, while their exact molecular and cellular mechanism are yet to be defined. We investigated the involvement of HDAC1 and eEF2 in the antidepressant mechanisms of fluoxetine using a lipopolysaccharide (LPS)-induced depression-like behavior model.

methodsFor in vivo analysis, mice were treated with LPS (2 mg/kg BW), fluoxetine (20 mg/kg BW), HDAC1 activator (Exifone: 54 mg/kg BW) and NH125 (1 mg/kg BW). Depressive-like behaviors were confirmed via behavior tests including OFT, FST, SPT, and TST. Cytokines were measured by ELISA while Iba-1 and GFAP expression were determined by immunofluorescence. Further, the desired gene expression was measured by immunoblotting. For in vitro analysis, BV2 cell lines were cultured; treated with LPS, exifone, and fluoxetine; collected; and analyzed.

resultsMice treated with LPS displayed depression-like behaviors, pronounced neuroinflammation, increased HDAC1 expression, and reduced eEF2 activity, as accompanied by altered synaptogenic factors including BDNF, SNAP25, and PSD95. Fluoxetine treatment exhibited antidepressant effects and ameliorated the molecular changes induced by LPS. Exifone, a selective HDAC1 activator, reversed the antidepressant and anti-inflammatory effects of fluoxetine both in vivo and in vitro, supporting a causing role of HDAC1 in neuroinflammation allied depression. Further molecular mechanisms underlying HDAC1 were explored with NH125, an eEF2K inhibitor, whose treatment reduced immobility time, altered pro-inflammatory cytokines, and NLRP3 expression. Moreover, NH125 treatment enhanced eEF2 and GSK3β activities, BDNF, SNAP25, and PSD95 expression, but had no effects on HDAC1.

conclusionsOur results showed that the antidepressant effects of fluoxetine may involve HDAC1-eEF2 related neuroinflammation and synaptogenesis.

Indexed as

AnimalsAntidepressive Agents, Second-GenerationCell LineDepressionDisease Models, AnimalElongation Factor 2 KinaseFluoxetineHistone Deacetylase 1LipopolysaccharidesMaleMiceMice, Inbred C57BLMicrogliaPhosphorylationAntidepressive Agents, Second-GenerationEef2k protein, mouseElongation Factor 2 KinaseFluoxetineHdac1 protein, mouseHistone Deacetylase 1LipopolysaccharidesDepressionFluoxetineHDAC1-eEF2NeuroinflammationSynaptogenesis

Identifiers

PMID33526073
PMCPMC7852137
OpenAlexW3126489438

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.