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Changes in Neuronal Excitability by Activated Microglia: Differential Na+ Current Upregulation in Pyramid-Shaped and Bipolar Neurons by TNF-α and IL-18

Overview of attention for article published in Frontiers in Neurology, March 2016
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Title
Changes in Neuronal Excitability by Activated Microglia: Differential Na+ Current Upregulation in Pyramid-Shaped and Bipolar Neurons by TNF-α and IL-18
Published in
Frontiers in Neurology, March 2016
DOI 10.3389/fneur.2016.00044
Pubmed ID
Authors

Lars Klapal, Birte A. Igelhorst, Irmgard D. Dietzel-Meyer

Abstract

Microglia are activated during pathological events in the brain and are capable of releasing various types of inflammatory cytokines. Here, we demonstrate that the addition of 5% microglia activated by 1 μg/ml lipopolysaccharides (LPS) to hippocampal cultures upregulates Na(+) current densities (INavD) of bipolar as well as pyramid-shaped neurons, thereby increasing their excitability. Deactivation of microglia by the addition of 10 ng/ml transforming growth factor-β (TGF-β) decreases INavD below control levels suggesting that the residual activated microglial cells influence neuronal excitability in control cultures. Preincubation of hippocampal cultures with 10 ng/ml tumor necrosis factor-α (TNF-α), a major cytokine released by activated microglia, upregulated INavD significantly by ~30% in bipolar cells, whereas in pyramid-shaped cells, the upregulation only reached an increase of ~14%. Incubation of the cultures with antibodies against either TNF-receptor 1 or 2 blocked the upregulation of INavD in bipolar cells, whereas in pyramid-shaped cells, increases in INavD were exclusively blocked by antibodies against TNF-receptor 2, suggesting that both cell types respond differently to TNF-α exposure. Since additional cytokines, such as interleukin-18 (IL-18), are released from activated microglia, we tested potential effects of IL-18 on INavD in both cell types. Exposure to 5-10 ng/ml IL-18 for 4 days increased INavD in both pyramid-shaped as well as bipolar neurons, albeit the dose-response curves were shifted to lower concentrations in bipolar cells. Our results suggest that by secretion of cytokines, microglial cells upregulate Na(+) current densities in bipolar and pyramid-shaped neurons to some extent differentially. Depending on the exact cytokine composition and concentration released, this could change the balance between the activity of inhibitory bipolar and excitatory pyramid-shaped cells. Since bipolar cells show a larger upregulation of INavD in response to TNF-α as well as respond to smaller concentrations of IL-18, our results offer an explanation for the finding, that in certain conditions of brain inflammations periods of dizziness are followed by epileptic seizures.

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Mendeley readers

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The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 27%
Student > Master 6 13%
Student > Bachelor 4 9%
Researcher 4 9%
Student > Doctoral Student 3 7%
Other 7 16%
Unknown 9 20%
Readers by discipline Count As %
Neuroscience 16 36%
Agricultural and Biological Sciences 7 16%
Biochemistry, Genetics and Molecular Biology 5 11%
Engineering 2 4%
Medicine and Dentistry 2 4%
Other 4 9%
Unknown 9 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 30 March 2016.
All research outputs
#18,449,393
of 22,858,915 outputs
Outputs from Frontiers in Neurology
#7,757
of 11,773 outputs
Outputs of similar age
#220,013
of 300,631 outputs
Outputs of similar age from Frontiers in Neurology
#45
of 61 outputs
Altmetric has tracked 22,858,915 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 11,773 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
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We're also able to compare this research output to 61 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.