Evidence map›Paper›PMID 30565903›Full record

ArticleJournal of psychiatry & neuroscience : JPN2019

ERβ agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy

Xu Hou, Samuel O. Adeosun, Xueying Zhao, Rosanne Hill, Baoying Zheng, Reveena Reddy, Xiao Su, Jeffrey Meyer, Thomas Mosley, Jun Ming Wang

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of psychiatry & neuroscience : JPN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. RETRACTED: Duloxetine, an SNRI, Targets pSTAT3 Signaling:International journal of molecular sciences · 2025
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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

10 authors at 4 institutions in 4 countries.

Xu HouFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Samuel O. AdeosunFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Xueying ZhaoFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Rosanne HillFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Baoying ZhengFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Reveena ReddyFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Xiao SuFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Jeffrey MeyerFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Thomas MosleyFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Jun Ming WangFrom the Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA (Hou, Wang); the Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA (Adeosun, Zhao, Zheng, Reddy, Wang); the Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA (Wang); the Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA (Mosley); the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Meyer); the Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (Zhao); and the College of Health & Biomedicine, Victoria University, Melbourne, Australia (Su).
Victoria University · AUUniversity of Toronto · CAHeilongjiang University of Chinese Medicine · CNUniversity of Mississippi Medical Center · US

Funding

Center for Psychiatric NeuroscienceP30GM103328 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI STOCKMEIER, CRAIG ALLEN · 2013 to 2017
$5.5M
NIGMS NIH HHS P30 GM103328
6 · The paper itself

Abstract

Background: Estrogen therapy (ET), an effective treatment for perimenopausal depression, often fails to ameliorate symptoms when initiated late after the onset of menopause. Our previous work has suggested that alternative splicing of RNA might mediate these differential effects of ET. Methods: Female Sprague–Dawley rats were treated with estradiol (E2) or vehicle 6 days (early ET) or 180 days (late ET) after ovariectomy (OVX). We investigated the differential expression of RNA splicing factors and tryptophan hydroxylase 2 (TPH2) protein using a customized RT2 Profiler PCR Array, reverse-transcription polymerase chain reaction, immunoprecipitation and behaviour changes in clinically relevant early and late ET. Results: Early ET, but not late ET, prolonged swimming time in the forced swim test and reduced anxiety-like behaviours in the elevated plus maze. It reversed OVX-increased (SFRS7 and SFRS16) or OVX-decreased (ZRSR2 and CTNNB1) mRNA levels of splicing factors and ERβ splicing changes in the brains of OVX rats. Early ET, but not late ET, also increased the expression of TPH2 and decreased monoamine oxidase A levels in the dorsal raphe in the brains of OVX rats. In late ET, only diarylpropionitrile (an ERβ-specific agonist) achieved similar results — not E2 (an ERα and ERβ agonist) or propylpyrazoletriol (an ERα-specific agonist). Limitations: Our experimental paradigm mimicked early and late ET in the clinical setting, but the contribution of age and OVX might be difficult to distinguish. Conclusion: These findings suggest that ERβ alternative splicing and altered responses in the regulatory system for serotonin may mediate the antidepressant efficacy of ET associated with the timing of therapy initiation. It is likely that ERβ-specific ligands would be effective estrogen-based antidepressants late after the onset of menopause.

Indexed as

AnimalsAntidepressive AgentsBrainEstradiolEstrogen Receptor betaFemaleImmobility Response, TonicMaze LearningMonoamine OxidaseNitrilesOvariectomyPhenolsPropionatesPyrazolesRatsRNA Splicing Factors2,3-bis(4-hydroxyphenyl)-propionitrile4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenolAntidepressive AgentsEstradiolEstrogen Receptor betaMonoamine OxidaseNitrilesPhenolsPropionatesPyrazolesRNA Splicing Factorstph2 protein, ratTryptophan Hydroxylase

Identifiers

PMID30565903
PMCPMC6306290
OpenAlexW2904101986

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.