Inhibition of microglial activation by amitriptyline and doxepin in interferon-\(\beta\) pre-treated astrocyte–microglia co-culture model of inflammation
- Depression may occur in patients with multiple sclerosis, especially during interferon-\(\beta\) (IFN-\(\beta\)) treatment, and therapy with antidepressants may be necessary. Interactions of IFN-\(\beta\) with antidepressants concerning glia-mediated inflammation have not yet been studied. Primary rat co-cultures of astrocytes containing 5% (M5, consistent with "physiological" conditions) or 30% (M30, consistent with "pathological, inflammatory" conditions) of microglia were incubated with 10 ng/mL amitriptyline or doxepin for 2 h, or with 2000 U/mL IFN-\(\beta\) for 22 h. To investigate the effects of antidepressants on IFN-\(\beta\) treatment, amitriptyline or doxepin was added to IFN-\(\beta\) pre-treated co-cultures. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to measure the glial cell viability, immunocytochemistry was performed to evaluate the microglial activation state, and ELISA was performed to measure pro-inflammatory TNF-\(\alpha\) and IL-6 cytokine concentrations. Incubation of inflammatory astrocyte–microglia co-cultures with amitriptyline, doxepin or IFN-\(\beta\) alone, or co-incubation of IFN-\(\beta\) pre-treated co-cultures with both antidepressants, significantly reduced the extent of inflammation, with the inhibition of microglial activation. TNF-\(\alpha\) and IL-6 levels were not affected. Accordingly, the two antidepressants did not interfere with the anti-inflammatory effect of IFN-\(\beta\) on astrocytes and microglia. Furthermore, no cytotoxic effects on glial cells were observed. This is the first in vitro study offering novel perspectives in IFN-\(\beta\) treatment and accompanying depression regarding glia.
Author: | Timo Jendrik FaustmannORCiDGND, Marisa WawrzyniakGND, Pedro FaustmannORCiDGND, Franco CorvaceGND, Fatme Seval IsmailORCiDGND |
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URN: | urn:nbn:de:hbz:294-105161 |
DOI: | https://doi.org/10.3390/brainsci13030493 |
Parent Title (English): | Brain sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/12/22 |
Date of first Publication: | 2023/03/15 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds amitriptyline; astrocyte-microglia co-culture model; depression; doxepin; inflammation; interferon-\(\beta\) |
Volume: | 13 |
Issue: | 3, Article 493 |
First Page: | 493-1 |
Last Page: | 493-18 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Institut für Anatomie, Abteilung für Neuroanatomie und molekulare Hirnforschung |
Knappschaftskrankenhaus Bochum, Klinik für Neurologie | |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |