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Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane

Overview of attention for article published in Journal of Neuroinflammation, January 2016
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  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

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Citations

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Title
Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane
Published in
Journal of Neuroinflammation, January 2016
DOI 10.1186/s12974-016-0505-y
Pubmed ID
Authors

Hernández-Rabaza, Vicente, Cabrera-Pastor, Andrea, Taoro-González, Lucas, Malaguarnera, Michele, Agustí, Ana, Llansola, Marta, Felipo, Vicente, Vicente Hernández-Rabaza, Andrea Cabrera-Pastor, Lucas Taoro-González, Michele Malaguarnera, Ana Agustí, Marta Llansola, Vicente Felipo

Abstract

Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE. Two main aims of this work were: (1) to assess whether chronic hyperammonemia increases inflammatory factors in the hippocampus and if this is associated with microglia and/or astrocytes activation and (2) to assess whether hyperammonemia-induced neuroinflammation in the hippocampus is associated with altered membrane expression of glutamate and GABA receptors and spatial learning impairment. There are no specific treatments for cognitive alterations in patients with MHE. A third aim was to assess whether treatment with sulforaphane enhances endogenous the anti-inflammatory system, reduces neuroinflammation in the hippocampus of hyperammonemic rats, and restores spatial learning and if normalization of receptor membrane expression is associated with learning improvement. We analyzed the following in control and hyperammonemic rats, treated or not with sulforaphane: (1) microglia and astrocytes activation by immunohistochemistry, (2) markers of pro-inflammatory (M1) (IL-1β, IL-6) and anti-inflammatory (M2) microglia (Arg1, YM-1) by Western blot, (3) membrane expression of GABA, AMPA, and NMDA receptors using the BS3 cross-linker, and (4) spatial learning using the radial maze. The results reported show that hyperammonemia induces astrocytes and microglia activation in the hippocampus, increasing pro-inflammatory cytokines IL-1β and IL-6. This is associated with altered membrane expression of AMPA, NMDA, and GABA receptors which would be responsible for altered neurotransmission and impairment of spatial learning in the radial maze. Treatment with sulforaphane promotes microglia differentiation from pro-inflammatory M1 to anti-inflammatory M2 phenotype and reduces activation of astrocytes in hyperammonemic rats. This reduces neuroinflammation, normalizes membrane expression of glutamate and GABA receptors, and restores spatial learning in hyperammonemic rats. Hyperammonemia-induced neuroinflammation impairs glutamatergic and GABAergic neurotransmission by altering membrane expression of glutamate and GABA receptors, resulting in impaired spatial learning. Sulforaphane reverses all these effects. Treatment with sulforaphane could be useful to improve cognitive function in cirrhotic patients with minimal or clinical hepatic encephalopathy.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
United States 1 2%
Unknown 57 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 24%
Unspecified 8 14%
Student > Master 8 14%
Student > Bachelor 7 12%
Student > Doctoral Student 6 10%
Other 16 27%
Readers by discipline Count As %
Neuroscience 16 27%
Unspecified 12 20%
Medicine and Dentistry 9 15%
Biochemistry, Genetics and Molecular Biology 8 14%
Agricultural and Biological Sciences 6 10%
Other 8 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 24 August 2017.
All research outputs
#5,860,458
of 11,648,047 outputs
Outputs from Journal of Neuroinflammation
#470
of 1,323 outputs
Outputs of similar age
#97,376
of 277,336 outputs
Outputs of similar age from Journal of Neuroinflammation
#32
of 70 outputs
Altmetric has tracked 11,648,047 research outputs across all sources so far. This one is in the 49th percentile – i.e., 49% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,323 research outputs from this source. They receive a mean Attention Score of 4.9. This one has gotten more attention than average, scoring higher than 64% 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 277,336 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 70 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 54% of its contemporaries.