Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice

Abstract

BackgroundOveractivated microglia is involved in various kinds of neurodegenerative diseases. Suppression of microglial overactivation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory effects of oxytocin (OT), which is a highly conserved nonapeptide with hormone and neurotransmitter properties, were investigated in vitro and in vivo.MethodsBV-2 cells and primary microglia were pre-treated with OT (0.1, 1, and 10 μM) for 2 h followed by LPS treatment (500 ng/ml); microglial activation and pro-inflammatory mediators were measured by Western blot, RT-PCR, and immunofluorescence. The MAPK and NF-κB pathway proteins were assessed by Western blot. The intracellular calcium concentration ([Ca2+]i) was determined using Fluo2-/AM assay. Intranasal application of OT was pre-treated in BALB/C mice (adult male) followed by injected intraperitoneally with LPS (5 mg/kg). The effect of OT on LPS-induced microglial activation and pro-inflammatory mediators was measured by Western blot, RT-PCR, and immunofluorescence in vivo.ResultsUsing the BV-2 microglial cell line and primary microglia, we found that OT pre-treatment significantly inhibited LPS-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, OT inhibited phosphorylation of ERK and p38 but not JNK MAPK in LPS-induced microglia. OT remarkably reduced the elevation of [Ca2+]i in LPS-stimulated BV-2 cells. Furthermore, a systemic LPS-treated acute inflammation murine brain model was used to study the suppressive effects of OT against neuroinflammation in vivo. We found that pre-treatment with OT showed marked attenuation of microglial activation and pro-inflammatory factor levels.ConclusionsTaken together, the present study demonstrated that OT possesses anti-neuroinflammatory activity and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

“…The GluN2B subunit of NMDA receptors is thought to exert a main channel function in the brain . Activation of NMDA receptors, including the GluN2B subunit, induces Ca 2+ influx, thus augmenting intracellular Ca 2+ levels and activating CaMKs . In the present study, we observed that ketamine reduced LPS‐induced Ca 2+ levels and CaMK II phosphorylation, thus inhibiting LPS‐mediated inflammation in BV2 cells.…”

An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period

“…Prolactin has been found to enhance the inflammatory response and proliferation of glia following a traumatic brain injury (Möderscheim et al, 2007), and oxytocin administration has been found to alleviate tissue damage in various animal models of injury (Akdemir et al, 2014; Houshmand et al, 2009; Karelina et al, 2011). The protective mechanisms by which prolactin and oxytocin act may be related to a decrease in pro-inflammatory cytokines from microglia, macrophages, and endothelial cells (Akman et al, 2015; Szeto et al, 2008; Tug˘tepe et al, 2013; Yuan et al, 2016). …”

Endoplasmic Reticulum Stress and NF-κB Pathway in Salidroside Mediated Neuroprotection: Potential of Salidroside in Neurodegenerative Diseases

“…In general, microglia play an important role in neuroprotection, especially confrontation with pathogens from the external environment; however, overexpression of microglia causes many key cellular responses that can cause diseases by inducing pro-inflammatory mediators such as NO, PGE 2 and TNF-α (Lee et al, 2011). Therefore, a promising therapeutic strategy used for neurodegenerative diseases was focused on blocking microglial activation processes (Kim and Joh, 2006;Yuan et al, 2016). Recently, numerous studies have reported that traditional Chinese medicine exert neuroprotective effects through suppressing microglial activation, and their effects have been elevated to have the potential to treat neurodegenerative diseases Wang et al, 2016).…”