Evidence map›Paper›PMID 27488351›Full record

ArticleMolecular brain2016

Sex-dependent adaptive changes in serotonin-1A autoreceptor function and anxiety in Deaf1-deficient mice.

Christine Luckhart, Tristan J Philippe, Brice Le François, Faranak Vahid-Ansari, Sean D Geddes, Jean-Claude Béïque, Diane C Lagace, Mireille Daigle, Paul R Albert

Open access · goldAbstract read
In one paragraph

Article in Molecular brain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Loss of Adult 5-HT1A Autoreceptors Results in a Paradoxical Anxiogenic Response to Antidepressant Treatment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017
    Article
  14. The adaptive brain in mental health: overcoming inherited risk factors.Journal of psychiatry & neuroscience : JPN · 2017
    Article
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

9 authors at 4 institutions in 1 country.

Christine LuckhartOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada.
Tristan J PhilippeOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada.
Brice Le FrançoisOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada.
Faranak Vahid-AnsariOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada.
Sean D GeddesDepartment of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON, K1H-8M5, Canada.
Jean-Claude BéïqueDepartment of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON, K1H-8M5, Canada.
Diane C LagaceDepartment of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON, K1H-8M5, Canada.
Mireille DaigleOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada.
Paul R AlbertOttawa Hospital Research Institute (Neuroscience), Ottawa, Canada. palbert@uottawa.ca.
Ottawa Hospital Research InstituteuOttawa Brain and Mind Research InstituteUniversity of Ottawa · CAOttawa Hospital · CA

Funding

CIHR 115098-1CIHR 123426-1CIHR MOP 115061
6 · The paper itself

Abstract

The C (-1019) G rs6295 promoter polymorphism of the serotonin-1A (5-HT1A) receptor gene is associated with major depression in several but not all studies, suggesting that compensatory mechanisms mediate resilience. The rs6295 risk allele prevents binding of the repressor Deaf1 increasing 5-HT1A receptor gene transcription, and the Deaf1-/- mouse model shows an increase in 5-HT1A autoreceptor expression. In this study, Deaf1-/- mice bred on a mixed C57BL6-BALB/c background were compared to wild-type littermates for 5-HT1A autoreceptor function and behavior in males and females. Despite a sustained increase in 5-HT1A autoreceptor binding levels, the amplitude of the 5-HT1A autoreceptor-mediated current in 5-HT neurons was unaltered in Deaf1-/- mice, suggesting compensatory changes in receptor function. Consistent with increased 5-HT1A autoreceptor function in vivo, hypothermia induced by the 5-HT1A agonist DPAT was augmented in early generation male but not female Deaf1-/- mice, but was reduced with succeeding generations. Loss of Deaf1 resulted in a mild anxiety phenotype that was sex-and test-dependent, with no change in depression-like behavior. Male Deaf1 knockout mice displayed anxiety-like behavior in the open field and light-dark tests, while female Deaf1-/- mice showed increased anxiety only in the elevated plus maze. These data show that altered 5-HT1A autoreceptor regulation in male Deaf1-/- mice can be compensated for by generational adaptation of receptor response that may help to normalize behavior. The sex dependence of Deaf1 function in mice is consistent with a greater role for 5-HT1A autoreceptors in sensitivity to depression in men.

Indexed as

Adaptation, PhysiologicalSex Characteristics8-Hydroxy-2-(di-n-propylamino)tetralinAnimalsAnxietyBehavior, AnimalDepressionDNA-Binding ProteinsFemaleHypothermia, InducedIon Channel GatingMaleMice, Inbred C57BLMice, KnockoutPhenotypeReceptor, Serotonin, 5-HT1A8-Hydroxy-2-(di-n-propylamino)tetralinDeaf1 protein, mouseDNA-Binding ProteinsReceptor, Serotonin, 5-HT1ASerotoninTranscription FactorsAnxietyMajor depressionRapheReceptor signalingSerotoninTransgenerational

Identifiers

PMID27488351
PMCPMC4973060
OpenAlexW2492212887

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.