ArticleResearch square2025
Polyinosinic polycytidylic acid (poly I:C) Induces Neuronal Cell Death Through NLRP3-mediated inflammasome in human microglia and neuroinflammation-induced cognitive impairment in mice.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Neuroinflammation and neuronal death are direct consequences of persistent microglial activation observed in many chronic neurological conditions. Activated microglia impact neuronal cells by releasing proinflammatory cytokines and inflammatory mediators, leading to neuronal damage and neurodegeneration. To investigate whether Polyinosinic polycytidylic acid (poly I:C), a synthetic double-stranded RNA molecule, induces neuroinflammation and neuronal death, we exposed microglia (HMC-3 cells) to poly I: C for 24 hrs, and assessed inflammatory cytokines. Additionally, to investigate whether poly(I:C) induces memory impairment and motor coordination deficits in C57BL/6 mice, we conducted a behavioural assessment and measured the expression of inflammatory cytokines in the brain. Poly (I:C) exposure significantly increased the mRNA and protein expression of inflammasome, proinflammatory cytokines (TNFα, IL-6, IL-1β, IL-8, IL-12, and IL-18) and chemokines in microglia. Poly (I: C) also significantly increased the translocation of NF-kB from the cytosol to the nucleus. Furthermore, the conditioned medium from poly(I:C)-treated cells markedly increased apoptosis in human neuronal cells (differentiated SHSY5Y cells) by activating pro-apoptotic markers, including Bax, Bad, cleaved caspase-3, cleaved PARP, and AIF. In mice, exposure to poly (I:C) significantly increased the mRNA expression of inflammatory cytokines, such as IL-6 and TNF-α, in the hippocampus. It also decreased the percentage of alternation in the T-maze test and reduced the distance travelled and average speed in the open field test, indicating motor and cognitive deficits. These findings suggest that poly (I:C) induces neuroinflammation through the inflammasome and proinflammatory mediators via the NLRP3/NF-κB signaling pathway in vitro and in vivo and induces motor and memory impairment in mice.
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