Evidence map›Paper›PMID 21309758›Full record

ArticleBritish journal of pharmacology2011

The Rho kinase inhibitor Fasudil up-regulates astrocytic glutamate transport subsequent to actin remodelling in murine cultured astrocytes.

C L Lau, R D O'Shea, B V Broberg, L Bischof, P M Beart

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

36 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Depression following traumatic brain injury in mice is associated with down-regulation of hippocampal astrocyte glutamate transporters by thrombin.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Astrocytic GAP43 Induced by the TLR4/NF-κB/STAT3 Axis Attenuates Astrogliosis-Mediated Microglial Activation and Neurotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    Article
  19. Review
  20. 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

5 authors at 5 institutions in 2 countries.

C L LauMolecular Neuropharmacology, Florey Neuroscience Institutes, Parkville, Australia.
R D O'Shea
B V Broberg
L Bischof
P M Beart
Commonwealth Scientific and Industrial Research Organisation · AUFlorey Institute of Neuroscience and Mental Health · AUGlostrup Hospital · DKLa Trobe University · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeGlutamate transporters play a major role in maintaining brain homeostasis and the astrocytic transporters, EAAT1 and EAAT2, are functionally dominant. Astrocytic excitatory amino acid transporters (EAATs) play important roles in various neuropathologies wherein astrocytes undergo cytoskeletal changes. Astrocytic plasticity is well documented, but the interface between EAAT function, actin and the astrocytic cytoskeleton is poorly understood. Because Rho kinase (ROCK) is a key determinant of actin polymerization, we investigated the effects of ROCK inhibitors on EAAT activity and astrocytic morphology. EXPERIMENTAL APPROACH: The functional activity of glutamate transport was determined in murine cultured astrocytes after exposure to the ROCK inhibitors Fasudil (HA-1077) and Y27632 using biochemical, molecular and morphological approaches. Cytochemical analyses assessed changes in astrocytic morphology, F-/G-actin, and localizations of EAAT1/2.

resultsFasudil and Y27632 increased [(3)H]-D-aspartate (D-Asp) uptake into astrocytes, and the action of Fasudil was time-dependent and concentration-related. The rapid stellation of astrocytes (glial fibrillary acidic protein immunocytochemistry) induced by Fasudil was accompanied by reduced phalloidin staining of F-actin and increased V(max) for [(3)H]-D-Asp uptake. Immunoblotting after biotinylation demonstrated that Fasudil increased the expression of EAAT1 and EAAT2 on the cell surface. Immunocytochemistry indicated that Fasudil induced prominent labelling of astrocytic processes by EAAT1/2. CONCLUSION AND IMPLICATIONS: These data show for the first time that ROCK plays a major role in determining the cell surface expression of EAAT1/2, providing new evidence for an association between transporter function and astrocytic phenotype. ROCK inhibitors, via the actin cytoskeleton, effect a consequent elevation of glutamate transporter function - this activity profile may contribute to their beneficial actions in neuropathologies.

Indexed as

1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineActinsAnimalsAspartic AcidAstrocytesBiological TransportCells, CulturedExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2Glial Fibrillary Acidic ProteinGlutamic AcidMiceMice, Inbred C57BLNerve Tissue ProteinsProsencephalonrho-Associated Kinases1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineActinsAspartic AcidExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2fasudilGlial Fibrillary Acidic Proteinglial fibrillary astrocytic protein, mouseGlutamic AcidNerve Tissue Proteinsrho-Associated KinasesSlc1a2 protein, mouseSlc1a3 protein, mouse

Identifiers

PMID21309758
PMCPMC3101616
OpenAlexW1560100279

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.