Evidence map›Paper›PMID 30352064›Full record

ArticlePloS one2018

Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice.

Yuxiao Chen, Marija Milenkovic, Wendy Horsfall, Ali Salahpour, Scott H Soderling, Amy J Ramsey

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. 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
0.1field-weighted citation impact, top 55% 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, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

6 authors at 2 institutions in 2 countries.

Yuxiao ChenDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-9493-7918
Marija MilenkovicDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Wendy HorsfallDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Ali SalahpourDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Scott H SoderlingDepartment of Cell Biology, Duke University Medical Center, Durham, NC, United States of America.
Amy J RamseyDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
University of Toronto · CADuke Medical Center · US

Funding

Molecular, Synaptic, and Circuit Basis for Schizophrenia-related PhenotypesR01MH103374 · NIMH · DUKE UNIVERSITY · PI SODERLING, SCOTT H · 2014 to 2018
$2.0M
NIMH NIH HHS R01 MH103374
6 · The paper itself

Abstract

NMDA receptors are important for cognition and are implicated in neuropsychiatric disorders. GluN1 knockdown (GluN1KD) mice have reduced NMDA receptor levels, striatal spine density deficits, and cognitive impairments. However, how NMDA depletion leads to these effects is unclear. Since Rho GTPases are known to regulate spine density and cognition, we examined the levels of RhoA, Rac1, and Cdc42 signaling proteins. Striatal Rac1-pathway components are reduced in GluN1KD mice, with Rac1 and WAVE-1 deficits at 6 and 12 weeks of age. Concurrently, medium spiny neuron (MSN) spine density deficits are present in mice at these ages. To determine whether WAVE-1 deficits were causal or compensatory in relation to these phenotypes, we intercrossed GluN1KD mice with WAVE-1 overexpressing (WAVE-Tg) mice to restore WAVE-1 levels. GluN1KD-WAVE-Tg hybrids showed rescue of striatal WAVE-1 protein levels and MSN spine density, as well as selective behavioral rescue in the Y-maze and 8-arm radial maze tests. GluN1KD-WAVE-Tg mice expressed normalized WAVE-1 protein levels in the hippocampus, yet spine density of hippocampal CA1 pyramidal neurons was not significantly altered. Our data suggest a nuanced role for WAVE-1 effects on cognition and a delineation of specific cognitive domains served by the striatum. Rescue of striatal WAVE-1 and MSN spine density may be significant for goal-directed exploration and associated long-term memory in mice.

Indexed as

Exploratory BehaviorMaze LearningAnimalsBehavior, AnimalCognitionCrosses, GeneticDendritic SpinesFemaleHippocampusMaleMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuropeptidesPhenotypeGprin1 protein, mouseNerve Tissue ProteinsNeuropeptidesrac1 GTP-Binding ProteinRac1 protein, mouseReceptors, N-Methyl-D-Aspartaterho GTP-Binding ProteinsWasf1 protein, mouseWiskott-Aldrich Syndrome Protein Family

Identifiers

PMID30352064
PMCPMC6198945
OpenAlexW2950120388

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.