Reduced Dpp expression accelerates inflammation-mediated neurodegeneration through activated glial cells during altered innate immune response in Drosophila

• Published in: Pesticide biochemistry and physiology Vol. 170; p. 104680
• Main Authors: Dalui, Shauryabrota, Chatterjee, Soumya, Sinha, Priyobrata, Bhattacharyya, Arindam
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2020
• Subjects: Decapentaplegic; Drosophila; Immune response; Neuroinflammation; Parkinson’'s disease; Neuroinflammation; Immune response; Parkinson’'s disease; Drosophila; Decapentaplegic
• ISSN: 0048-3575; 1095-9939
• DOI: 10.1016/j.pestbp.2020.104680

The progression of neurodegenerative disease is very complex biological process and the molecular crosstalk of inflammatory cytokines during neurodegeneration is associated with multiple cascade signalling. Few evidences suggest that environmental toxin, Paraquat (PQ) administration activates the microglia and intensify the release of proinflamatory cytokines during progression of Parkinson’'s disease (PD) but the proper aetiology remained unknown. However, the fundamental role of anti-inflammatory molecule Decapentaplegic (Dpp), homologue of the secreted mammalian Transforming growth factor-β (TGF-β) signalling molecule during neurodegeneration of invertebrate fly model is yet to establish. To elucidate the molecular processes during early stage of Parkinson's disease, we observed neuro-toxin plays a determining role in the increased vulnerability to a particular PQ exposure that is attended by decreased lifespan, severe locomotor deficits, and more loss of dopaminergic (DA) neuron in PQ-treated Dpp deficient fly than wild type (WT). Simultaneously, activated microglia induced the inflammatory response with the release of pro-inflammatory and anti-inflammatory cytokine in Drosophila during neurodegeneration. Moreover, neuro-toxin exposure altered the expression of innate immune genes in both WT and mutant fly compared to the respective PQ-treated flies. Interestingly, PQ exposure reduced the expression of innate immune genes in mutant fly compared to WT. It may indicate that PQ exposure had broken down the immune defence response in mutant fly than WT whereas, without PQ exposure the innate immune tolerance level was higher in fly with reduced Dpp expression than WT. Thus, we observed the conserve anti-inflammatory factor TGF-β may exhibit a crucial defensive role during inflammation mediated neurodegeneration in invertebrate Drosophila melanogaster. [Display omitted] •Paraquat (PQ) administration aggravated the more neurodegeneration in Decapentaplegic (Dpp) deficient Drosophila than WT.•Glial activation altered the level of inflammatory cytokines in both reduced Dpp expression and wild type flies.•PQ-intoxication exhibited dopaminergic neuronal loss in both the fly types.•Immune defence responsive genes were down- and up regulated with and without PQ-exposure in both types of fly respectively•The conserved anti-inflammatory function was observed within invertebrate during neurodegeneration.