Evidence map›Paper›PMID 21215386›Full record

ArticleBiological psychiatry2011

Short-hairpin RNA silencing of endogenous fibroblast growth factor 2 in rat hippocampus increases anxiety behavior.

Emine Eren-Koçak, Cortney A Turner, Stanley J Watson, Huda Akil

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

35 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  3. Review
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  7. Review
  8. Growth Factors and Alcohol Use Disorder.Cold Spring Harbor perspectives in medicine · 2020
    Review
  9. Article
  10. Article
  11. Fibroblast Growth Factors in Depression.Frontiers in pharmacology · 2019
    Review
  12. Fgf9Molecular neurobiology · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Fibroblast growth factor 9 is a novel modulator of negative affect.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Emine Eren-KoçakInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Cortney A Turner
Stanley J Watson
Huda Akil
University of Michigan–Ann Arbor · USHacettepe University · TR

Funding

MICHIGAN INSTITUTE FOR CLINICAL AND HEALTH RESEARCH (MICHR) (UL1): (BPCA)UL1RR024986 · NCRR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHANLEY, THOMAS P. · 2007 to 2011
$51.2M
Project 5: High-Throughput Analysis of Gene RegulationP50MH060398 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUNNEY, WILLIAM E · 1999 to 2008
$12.7M
FOREBRAIN OVEREXPRESSION OF A STRESS-RELATED GENEP01DA021633 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AKIL, HUDA · 2007 to 2011
$6.2M
NCRR NIH HHS UL1 RR024986NCRR NIH HHS UL1RR024986NIDA NIH HHS 5P01DA021633-02NIDA NIH HHS P01 DA021633NIMH NIH HHS L99MH60398NIMH NIH HHS P50 MH060398
6 · The paper itself

Abstract

backgroundThe fibroblast growth factor system has been implicated in the pathophysiology of mood disorders in humans and in affective behavior in animal models. However, the studies have been either correlative or involved exogenous administration of fibroblast growth factor 2 (FGF2). None of them have directly linked endogenous FGF2 to changes in emotional responses. Therefore, we began a series of studies to knockdown FGF2 by RNA interference to examine the role of brain FGF2 in emotional responsiveness.

methodsWe assessed the efficacy of short-hairpin RNA (shRNA) sequences targeted to FGF2 in COS7 cells transfected with a plasmid vector containing the full-length FGF2 sequence. We then sought to assess the effects of knocking down FGF2 gene expression in vivo on behavior. We microinjected a lentiviral vector containing either a shRNA targeting FGF2 or a nonsilencing sequence bilaterally into the dentate gyrus of the rat.

resultsIn a reporter assay system, three different shRNA sequences resulted in significant FGF2 knockdown in vitro. Five weeks following a single microinjection of one of those sequences in vivo, we observed a significant decrease in FGF2 gene expression by messenger RNA in situ hybridization in the hippocampus. The FGF2 knockdown increased the time spent in the closed arms of the elevated-plus maze, a test of anxiety behavior.

conclusionsThe FGF2 knockdown in the hippocampus resulted in an anxiogenic effect. Together with our findings of an inverse correlation between anxiety and FGF2 expression levels, these results implicate FGF2 in the genesis and expression of anxiety disorders.

Indexed as

AnimalsAnxietyChlorocebus aethiopsCOS CellsDisease Models, AnimalFibroblast Growth Factor 2Gene Expression RegulationHippocampusMaleMaze LearningMicroinjectionsRatsRats, Sprague-DawleyRNA, Small InterferingTransfectionFibroblast Growth Factor 2RNA, Small Interfering

Identifiers

PMID21215386
PMCPMC3046217
OpenAlexW2003469897

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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.