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.
Author: | Lars KlapalGND, Birte IgelhorstGND, Irmgard D. Dietzel-MeyerORCiDGND |
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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): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |