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Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of…

Overview of attention for article published in Journal of Neuroinflammation, April 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

Mentioned by

news
1 news outlet

Citations

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60 Dimensions

Readers on

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81 Mendeley
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Title
Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia
Published in
Journal of Neuroinflammation, April 2016
DOI 10.1186/s12974-016-0549-z
Pubmed ID
Authors

Vicente Hernandez-Rabaza, Andrea Cabrera-Pastor, Lucas Taoro-Gonzalez, Alba Gonzalez-Usano, Ana Agusti, Tiziano Balzano, Marta Llansola, Vicente Felipo

Abstract

Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them. We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane expression, extracellular GABA, glutamate-nitric oxide-cGMP pathway, and learning and motor coordination. Neuroinflammation increases GABAergic tone in the cerebellum by increasing GAT-3 membrane expression. This impairs motor coordination and learning in the Y maze. Sulforaphane could be a new therapeutic approach to improve cognitive and motor function in hyperammonemia, hepatic encephalopathy, and other pathologies associated with neuroinflammation by promoting microglia differentiation from M1 to M2.

Mendeley readers

The data shown below were compiled from readership statistics for 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Unknown 80 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 21%
Student > Master 12 15%
Researcher 10 12%
Student > Bachelor 7 9%
Student > Doctoral Student 6 7%
Other 13 16%
Unknown 16 20%
Readers by discipline Count As %
Neuroscience 22 27%
Medicine and Dentistry 11 14%
Agricultural and Biological Sciences 9 11%
Biochemistry, Genetics and Molecular Biology 6 7%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Other 5 6%
Unknown 24 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 April 2016.
All research outputs
#1,039,950
of 7,588,328 outputs
Outputs from Journal of Neuroinflammation
#178
of 981 outputs
Outputs of similar age
#53,708
of 266,862 outputs
Outputs of similar age from Journal of Neuroinflammation
#21
of 60 outputs
Altmetric has tracked 7,588,328 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 981 research outputs from this source. They receive a mean Attention Score of 4.6. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,862 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 78% of its contemporaries.
We're also able to compare this research output to 60 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.