Changes in neuronal excitability by activated microglia

  • 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 \(\mu\)g/ml lipopolysaccharides (LPS) to hippocampal cultures upregulates \(Na^{+}\) current densities (\(I_{NavD}\)) 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-\(\beta\) (TGF-\(\beta\)) decreases \(I_{NavD}\) 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-\(\alpha\) (TNF-\(\alpha\)), a major cytokine released by activated microglia, upregulated \(I_{NavD}\) 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 \(I_{NavD}\) in bipolar cells, whereas in pyramid-shaped cells, increases in \(I_{NavD}\) were exclusively blocked by antibodies against TNF-receptor 2, suggesting that both cell types respond differently to TNF-\(\alpha\) exposure. Since additional cytokines, such as interleukin-18 (IL-18), are released from activated microglia, we tested potential effects of IL-18 on \(I_{NavD}\) in both cell types. Exposure to 5–10 ng/ml IL-18 for 4 days increased \(I_{NavD}\) 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 \(I_{NavD}\) in response to TNF-\(\alpha\) 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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Metadaten
Author:Lars KlapalGND, Birte IgelhorstGND, Irmgard D. Dietzel-MeyerORCiDGND
URN:urn:nbn:de:hbz:294-57853
DOI:https://doi.org/10.3389/fneur.2016.00044
Parent Title (English):Frontiers in neurology
Subtitle (English):differential \(Na^{+}\) current upregulation in pyramid-shaped and bipolar neurons by TNF-\(\alpha\) and IL-18
Document Type:Article
Language:English
Date of Publication (online):2018/06/28
Date of first Publication:2016/03/30
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds; glial cells; lipopolysaccharide; transforming growth factor-\(\beta\)
hippocampal neurons; interleukin-18; microglia; tumor necrosis factor-\(\alpha\); voltage-activated sodium currents
Volume:7
First Page:44-1
Last Page:44-13
Note:
Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum.
Note:
Frontiers in Neurology, Volume 7, Artikelnummer 44
Institutes/Facilities:Lehrstuhl Biochemie II, Molekulare Biochemie
Dewey Decimal Classification:Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie
open_access (DINI-Set):open_access
faculties:Fakultät für Chemie und Biochemie
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International