Evidence map›Paper›PMID 25662838›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice.

Tomomi Aida, Junichi Yoshida, Masatoshi Nomura, Asami Tanimura, Yusuke Iino, Miho Soma, Ning Bai, Yukiko Ito, Wanpeng Cui, Hidenori Aizawa and 9 more

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

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
6.6field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 154 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
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  10. Astrocytes in Rodent Anxiety-Related Behavior: Role of Calcium and Beyond.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Glia Development and Function in the NematodeCold Spring Harbor perspectives in biology · 2024
    Review
  15. Astrocytic RARγ mediates hippocampal astrocytosis and neurogenesis deficits in chronic retinoic acid-induced depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  16. Article
  17. Article
  18. Review
  19. Article
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23 more citing papers are in PubMed but not listed here.

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

19 authors at 7 institutions in 2 countries.

Tomomi AidaLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Junichi YoshidaLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Masatoshi NomuraDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Asami TanimuraDepartment of Neurophysiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Yusuke IinoLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Miho SomaLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Ning BaiLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Yukiko ItoLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Wanpeng CuiLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Hidenori AizawaLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Michiko YanagisawaLaboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Terumi NagaiLaboratory for Neuron-Glia Circuitry, Brain Science Institute, RIKEN, Saitama, Japan.
Norio TakataLaboratory for Neuron-Glia Circuitry, Brain Science Institute, RIKEN, Saitama, Japan.
Kenji F TanakaDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Ryoichi TakayanagiDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masanobu KanoDepartment of Neurophysiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Magdalena GötzPhysiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany.
Hajime HiraseDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Kohichi Tanaka1] Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan [2] JST, CREST, Saitama, Japan [3] The Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo, Japan.
Tokyo Medical and Dental University · JPKeio University · JPKyushu University · JPRIKEN Center for Brain Science · JPThe University of Tokyo · JPJapan Science and Technology Agency · JPLudwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An increase in the ratio of cellular excitation to inhibition (E/I ratio) has been proposed to underlie the pathogenesis of neuropsychiatric disorders, such as autism spectrum disorders (ASD), obsessive-compulsive disorder (OCD), and Tourette's syndrome (TS). A proper E/I ratio is achieved via factors expressed in neuron and glia. In astrocytes, the glutamate transporter GLT1 is critical for regulating an E/I ratio. However, the role of GLT1 dysfunction in the pathogenesis of neuropsychiatric disorders remains unknown because mice with a complete deficiency of GLT1 exhibited seizures and premature death. Here, we show that astrocyte-specific GLT1 inducible knockout (GLAST(CreERT2/+)/GLT1(flox/flox), iKO) mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes. Electrophysiological studies reveal that excitatory transmission at corticostriatal synapse is normal in a basal state but is increased after repetitive stimulation. Furthermore, treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated the pathological repetitive behaviors in iKO mice. These results suggest that astroglial GLT1 has a critical role in controlling the synaptic efficacy at corticostriatal synapses and its dysfunction causes pathological repetitive behaviors.

Indexed as

AnimalsAnimals, NewbornAnxietyCerebral CortexCumulative Trauma DisordersDisease Models, AnimalEnzyme InhibitorsExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2Excitatory Postsynaptic PotentialsFemaleGene Expression RegulationHyperalgesiaMaleMiceMice, TransgenicEnzyme InhibitorsExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2Nerve Tissue ProteinsProteinsROSA22 protein, mouseSlc1a2 protein, mouse

Identifiers

PMID25662838
PMCPMC4915262
OpenAlexW2035077079

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.