Evidence map›Paper›PMID 26499511›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016

A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice.

Liang Zhang, Robert G Wither, Min Lang, Chiping Wu, Elena Sidorova-Darmos, Hristo Netchev, Catherine B Matolcsy, Orlando Carter Snead, James H Eubanks

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

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. 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
0.7field-weighted citation impact, top 21% 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, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
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 2 institutions in 1 country.

Liang ZhangDivision of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Robert G WitherDivision of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Min LangUniversity of Toronto Epilepsy Research Program, University of Toronto, Toronto, ON, Canada.
Chiping WuDivision of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Elena Sidorova-DarmosDivision of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Hristo NetchevDivision of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Catherine B MatolcsyDivision of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Orlando Carter SneadUniversity of Toronto Epilepsy Research Program, University of Toronto, Toronto, ON, Canada.
James H EubanksUniversity of Toronto Epilepsy Research Program, University of Toronto, Toronto, ON, Canada.
University Health Network · CAUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research MOP-81104
6 · The paper itself

Abstract

Cortical network hyper-excitability is a common phenotype in mouse models lacking the transcriptional regulator methyl-CPG-binding protein 2 (MeCP2). Here, we implicate enhanced GABAB receptor activity stemming from diminished cortical expression of the GABA transporter GAT-1 in the genesis of this network hyper-excitability. We found that administering the activity-dependent GABAB receptor allosteric modulator GS-39783 to female Mecp2(+/-) mice at doses producing no effect in wild-type mice strongly potentiated their basal rates of spontaneous cortical discharge activity. Consistently, administering the GABAB receptor antagonist CGP-35348 significantly decreased basal discharge activity in these mice. Expression analysis revealed that while GABAB or extra-synaptic GABAA receptor prevalence is preserved in the MeCP2-deficient cortex, the expression of GAT-1 is significantly reduced from wild-type levels. This decrease in GAT-1 expression is consequential, as low doses of the GAT-1 inhibitor NO-711 that had no effects in wild-type mice strongly exacerbated cortical discharge activity in female Mecp2(+/-) mice. Taken together, these data indicate that the absence of MeCP2 leads to decreased cortical levels of the GAT-1 GABA transporter, which facilitates cortical network hyper-excitability in MeCP2-deficient mice by increasing the activity of cortical GABAB receptors.

Indexed as

Action PotentialsAnimalsCerebral CortexCyclopentanesElectrodes, ImplantedElectroencephalographyFemaleGABA Plasma Membrane Transport ProteinsGABA Uptake InhibitorsMaleMethyl-CpG-Binding Protein 2MiceMice, Inbred C57BLOrganophosphorus CompoundsPyrimidinesCGP 35348CyclopentanesGABA Plasma Membrane Transport ProteinsGABA Uptake InhibitorsMecp2 protein, mouseMethyl-CpG-Binding Protein 2N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamineOrganophosphorus CompoundsPyrimidinesSlc6a1 protein, mouse

Identifiers

PMID26499511
PMCPMC4832024
OpenAlexW2314951881

What OpenQuestion holds

Textmetadata
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.