Evidence map›Paper›PMID 26037489›Full record

ArticleThe international journal of neuropsychopharmacology2015

Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice.

Kerin K Higa, Baohu Ji, Mahalah R Buell, Victoria B Risbrough, Susan B Powell, Jared W Young, Mark A Geyer, Xianjin Zhou

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

Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 50% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
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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

8 authors at 2 institutions in 1 country.

Kerin K HigaDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Baohu JiDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Mahalah R BuellDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Victoria B RisbroughDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Susan B PowellDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Jared W YoungDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Mark A GeyerDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa).
Xianjin ZhouDepartment of Psychiatry, University of California San Diego, La Jolla, CA (Ms Higa, Drs Ji, Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Research Service, VA San Diego Healthcare System, La Jolla, CA (Drs Risbrough, Powell, Young, Geyer, and Zhou, and Ms Buell); Neurosciences Graduate Program, University of California San Diego, La Jolla, CA (Ms Higa). xzhou@ucsd.edu.
University of California, San Diego · USVA San Diego Healthcare System · US

Funding

Neurosciences Graduate Training ProgramT32NS061847 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Brenda L Bloodgood · 2008 to 2026
$7.7M
Sp4 Pathway in the Modulation of Sensorimotor Gating and MemoryR01MH073991 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHOU, XIANJIN · 2006 to 2014
$2.9M
Role of COMTval158met in PTSD risk and treatment responseI01BX002558 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI RISBROUGH, VICTORIA B · 2015 to 2018
–
BLRD VA I01 BX002558NIMH NIH HHS R01 MH073991NIMH NIH HHS R01MH073991NINDS NIH HHS T32 NS061847
6 · The paper itself

Abstract

backgroundKetamine produces schizophrenia-like behavioral phenotypes in healthy people. Prolonged ketamine effects and exacerbation of symptoms after the administration of ketamine have been observed in patients with schizophrenia. More recently, ketamine has been used as a potent antidepressant to treat patients with major depression. The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Sp4 is a transcription factor for which gene expression is restricted to neuronal cells in the brain. Our previous studies demonstrated that Sp4 hypomorphic mice display several behavioral phenotypes relevant to psychiatric disorders, consistent with human SP4 gene associations with schizophrenia, bipolar disorder, and major depression. Among those behavioral phenotypes, hypersensitivity to ketamine-induced hyperlocomotion has been observed in Sp4 hypomorphic mice.

methodsIn the present study, we used the Cre-LoxP system to restore Sp4 gene expression, specifically in either forebrain excitatory or GABAergic inhibitory neurons in Sp4 hypomorphic mice. Mouse behavioral phenotypes related to psychiatric disorders were examined in these distinct rescue mice.

resultsRestoration of Sp4 in forebrain excitatory neurons did not rescue deficient sensorimotor gating nor ketamine-induced hyperlocomotion. Restoration of Sp4 in forebrain GABAergic neurons, however, rescued ketamine-induced hyperlocomotion, but did not rescue deficient sensorimotor gating.

conclusionsOur studies suggest that the Sp4 gene in forebrain GABAergic neurons regulates ketamine-induced hyperlocomotion.

Indexed as

Akathisia, Drug-InducedAnimalsCohort StudiesExcitatory Amino Acid AntagonistsFemaleGABAergic NeuronsKetamineMaleMice, 129 StrainMice, TransgenicProsencephalonSensory GatingSp4 Transcription FactorExcitatory Amino Acid AntagonistsKetamineSp4 protein, mouseSp4 protein, ratSp4 Transcription FactorGABAergicgenetic rescueketaminelocomotor activitySp4

Identifiers

PMID26037489
PMCPMC4756721
OpenAlexW2249872916

What OpenQuestion holds

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LicenceCC BY-NC
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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.