Objective: To understand the differential susceptibility of neuronal and glial populations to lipopolysaccharide (LPS) mediated insult in an animal model of PD. Also, to test the efficacy of apocyanin, a NADPH oxidase inhibitor and curcumin in modulating glial and neuronal response in LPS induced PD model

Background: Converging lines of evidence suggest that glia associated neuroinflammatory processes may account for the progressive death of dopaminergic neurons in Parkinson’s disease (PD). Recent studies have also highlighted that glial and neuronal cultures behave differently to a toxic insult and suggests a protective role of glial cells in case of neurotoxicity. Also, Apocyanin, an established microglial NADPH oxidase inhibitor and curcumin has been proved to have beneficial effects in modulating anti-inflammatory as well as anti-oxidative effects in case of lipopolysaccharide induced PD model.

Methods: LPS (5µg/kg b.wt) was injected intranigral using a digital stereotaxic apparatus. Apocyanin (10mg/kg/ day) and curcumin (40mg/kg b.wt) was administered beginning form day 1 of LPS injection intraperitoneally daily for a period of 21 days. At the end of experiment glial and neuronal population was isolated from mid brain region of rat brain.

Results: Following LPS injection significant augmentation in the gene as well as protein expression of transcription factor NFκB as well as proinflammatory cytokines (TNF-α, IL-1α, IL-1β), NADPH oxidase subunits gp91PHOX and gp21PHOX were observed in the glial as well as neuronal fractions thus suggesting the prevalence of inflammatory responses and activation of NADPH oxidase complex. With this significantly compromised glutathione system as well as other antioxidant enzymes (SOD, Catalase), total ROS production were observed in neuronal and glial fraction. It was analysed that inflammatory and oxidative stress markers in case of glial population was severely altered in comparison to neuronal population. With apocyanin and curcumin treatment marked improvement in inflammatory as well as oxidative stress markers were observed in case of neuronal and glial population.

Conclusions: This can be concluded that apocyanin and curcumin both play an important role in modulating glial cell functions thus revealing its potential anti-inflammatory role along with its NADPH oxidase inhibiting property. Study also suggests a protective role of glial cells by upregulating their transcriptional factors and oxidative stress markers in order to protect neurons against LPS insult. Therefore, its neuroprotective role could be further evaluated in other toxicological conditions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differential-glial-and-neuronal-response-in-lipopolysaccharide-induced-parkinsons-disease-model-modulation-with-apocyanin-and-curcumin/