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Maprotiline ameliorates isoflurane-induced microglial activation via regulating triggering receptor expressed in myeloid cells 2 (TREM2)
Maprotiline ameliorates isoflurane-induced microglial activation via regulating triggering receptor expressed in myeloid cells 2 (TREM2)
- Source :
- Bioengineered, Vol 12, Iss 2, Pp 12332-12344 (2021), Bioengineered, article-version (VoR) Version of Record
- Publication Year :
- 2021
- Publisher :
- Taylor & Francis Group, 2021.
-
Abstract
- Isoflurane-induced neurotoxicity has attracted much interest. Recent studies suggest that isoflurane causes microglial activation, resulting in an inflammatory response and microglial insult. Maprotiline is a novel drug that has been licensed as an antidepressant with considerable anti-inflammatory activity. However, it is still unknown whether maprotiline possesses a protective effect against isoflurane-induced microglial insult. Here, we found that maprotiline ameliorated isoflurane-caused reduction in BV2 microglial cell viability and lactate dehydrogenase (LDH) release. Maprotiline mitigated isoflurane-induced oxidative stress by inhibiting reactive oxygen species (ROS) production and increasing superoxide dismutase (SOD) activity. Isoflurane-induced expression and production of inflammatory markers including tumor necrosis factor (TNF-α), interleukin (IL)-1β, cyclooxygenase‐2 (COX-2), and prostaglandin E2 (PGE2) were decreased in maprotiline-treated cells. Maprotiline inhibited the mRNA and protein levels of Iba1, a marker of microglial activation, in isoflurane-induced BV2 cells. Maprotiline treatment restored isoflurane-induced reduction of TREM2 in BV2 microglial cells. In addition, the knockdown of TREM2 abolished the beneficial effects of maprotiline against isoflurane. Collectively, maprotiline exerted protective effects against isoflurane-caused oxidative stress, inflammatory response, and cell injury via regulating TREM2. These findings show that maprotiline prevented the isoflurane-induced microglial activation, indicating that maprotiline might be used as an optimal therapeutic agent for preventing the isoflurane-caused neurotoxicity.
- Subjects :
- Cell Survival
Bioengineering
Applied Microbiology and Biotechnology
Dinoprostone
Mice
isoflurane
Animals
oxidative stress
Myeloid Cells
Receptors, Immunologic
microglial activation
Cells, Cultured
Membrane Glycoproteins
L-Lactate Dehydrogenase
Superoxide Dismutase
trem2
General Medicine
Cyclooxygenase 2
inflammation
maprotiline
Microglia
Reactive Oxygen Species
Biomarkers
TP248.13-248.65
Research Article
Research Paper
Signal Transduction
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 21655987 and 21655979
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Bioengineered
- Accession number :
- edsair.doi.dedup.....a767aa5f66c85ed990cdd26449a0e6da