Evidence map›Paper›PMID 37990254›Full record

ArticleCell & bioscience2023

Captive ERVWE1 triggers impairment of 5-HT neuronal plasticity in the first-episode schizophrenia by post-transcriptional activation of HTR1B in ALKBH5-m6A dependent epigenetic mechanisms.

Xiulin Wu, Lianzhong Liu, Xing Xue, Xuhang Li, Kexin Zhao, Jiahang Zhang, Wenshi Li, Wei Yao, Shuang Ding, Chen Jia and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

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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

17 citing papers in PubMed, 15 citations in OpenAlex.

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  15. Neuroplasticity in the transition from acute to chronic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
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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 at 1 institution in 1 country.

Xiulin WuState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Lianzhong LiuWuhan Mental Health Center, Wuhan, 430071, China.
Xing XueState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Xuhang LiState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Kexin ZhaoState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Jiahang ZhangState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Wenshi LiState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Wei YaoState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Shuang DingState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Chen JiaState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Fan ZhuState Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China. fanzhu@whu.edu.cn.ORCID http://orcid.org/0000-0001-7031-2956
Wuhan University · CN

Funding

Fundamental Research Funds for the Central Universities 2042023kf0230National Natural Science Foundation of China 81971943National Natural Science Foundation of China 82272321Stanley Foundation 06R-1366
6 · The paper itself

Abstract

backgroundAbnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia.

resultsHTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1.

conclusionsOverall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.

Indexed as

ALKBH5ERVWE1HTR1BSchizophreniaSynaptic plasticity

Identifiers

PMID37990254
PMCPMC10664518
OpenAlexW4388868610

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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.