Evidence map›Paper›PMID 33542258›Full record

ArticleScientific reports2021

Elevated preoptic brain activity in zebrafish glial glycine transporter mutants is linked to lethargy-like behaviors and delayed emergence from anesthesia.

Michael J Venincasa, Owen Randlett, Sureni H Sumathipala, Richard Bindernagel, Matthew J Stark, Qing Yan, Steven A Sloan, Elena Buglo, Qing Cheng Meng, Florian Engert and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. 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
0.6field-weighted citation impact, top 38% 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, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

14 authors at 6 institutions in 2 countries.

Michael J VenincasaDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Owen RandlettDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA.
Sureni H SumathipalaDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Richard BindernagelDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Matthew J StarkDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Qing YanDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Steven A SloanDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Elena BugloDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Qing Cheng MengDepartments of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Florian EngertDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA.
Stephan ZüchnerJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, 33101, USA.
Max B KelzDepartments of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sheyum SyedDepartment of Physics, University of Miami, Coral Gables, FL, 33146, USA.
Julia E DallmanDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA. j.dallman@miami.edu.
University of Miami · USUniversity of Pennsylvania · USDr. John T. Macdonald Foundation · USEmory University · USHarvard University · USUniversité Claude Bernard Lyon 1 · FR

Funding

Zooming into the fish's brain-What is really going on! Connectomics analysis of larval zebrafish.U19NS104653 · NINDS · HARVARD UNIVERSITY · PI Randal Burns, Florian Engert · 2017 to 2026
$39.4M
Analysis of the shocked zebrafish motility mutantK01NS048200 · NINDS · UNIVERSITY OF MIAMI CORAL GABLES · PI DALLMAN, JULIA EVE · 2004 to 2009
$499k
Gastrointestinal Comorbidities in Autism Spectrum DisordersR21HD093021 · NICHD · UNIVERSITY OF MIAMI CORAL GABLES · PI DALLMAN, JULIA EVE · 2018 to 2019
$403k
NICHD NIH HHS R21 HD093021NIH HHS K01NS048200NIH HHS U19NS104653NINDS NIH HHS K01 NS048200NINDS NIH HHS U19 NS104653
6 · The paper itself

Abstract

Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter (glyt1 - / -) mutant model. We compared locomotor behaviors; dose-response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1-/- mutants and their siblings. To identify differentially active brain regions in glyt1-/- mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1-/- mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose-response curves, glyt1-/- mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1-/- mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1-/- mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1-/- mutants.

Indexed as

AminobenzoatesAnesthesia, GeneralAnestheticsAnimalsAnimals, Genetically ModifiedCraniotomyDelayed Emergence from AnesthesiaDisease Models, AnimaleIF-2 KinaseGene ExpressionGlycineGlycine Plasma Membrane Transport ProteinsHyperglycinemia, NonketoticKetamineLocomotionNeuronsAminobenzoatesAnestheticseIF-2 KinaseGlycineGlycine Plasma Membrane Transport ProteinsKetaminePropofolSLC6A9 protein, zebrafishtricaineZebrafish Proteins

Identifiers

PMID33542258
PMCPMC7862283
OpenAlexW3127662776

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.