Quercetin suppress microglial neuroinflammatory response and induce antidepressent-like effect in olfactory bulbectomized rats

Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, INDIA.
Neuroscience (Impact Factor: 3.36). 10/2013; 255. DOI: 10.1016/j.neuroscience.2013.09.044
Source: PubMed


In rodents, olfactory bulbectomy (OBX) results in several behavioral and biochemical changes, useful as a screening model for antidepressants. Recent evidences suggest that quercetin; a bioflavonoid exhibits a variety of behavioral effects including anxiolytic, antidepressant, etc. Since microglia are commonly implicated in the neuroinflammation cascade of depression, we hypothesized that quercetin might involve microglial inhibition pathway in its antidepressant-like effects. To support such a possibility, we investigated the interaction of quercetin with a known microglial inhibitor (minocycline) against olfactory bulbectomy induced depression in male Wistar rats. In our study, ablation of olfactory bulbs caused hyperactivity in open field arena and increased immobility time in forced swim test which was coupled with enhanced serum corticosterone levels. Additionally, there were increased oxidative-nitrosative stress markers, inflammatory mediators (TNF-α and IL-6) along with enhanced apoptotic factor (caspase-3) in both cerebral cortex and hippocampal brain regions of OBX animals. These results were further supported by reports from histopathological analysis. After a surgical recovery period of two weeks, treatment with quercetin (40, 80 mg/kg; p.o., 14 days) significantly prevented OBX-induced behavioral, biochemical, molecular and histopathological alterations. Further, combination of sub effective doses of quercetin (20, 40 mg/kg; p.o.) with minocycline (25 mg/kg; p.o.) significantly potentiated their protective effects as compared to their effects alone. Based on our results, we propose that microglial inhibitory pathway might be involved in the neuroprotective effects of quercetin and suppression of oxidative-nitrosative stress mediated neuroinflammation- apoptotic cascade associated with olfactory bulbectomy rat model of depression.

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