Inhibition of NLRP3 inflammasome alleviates cognitive deficits in a mouse model of anti-NMDAR encephalitis induced by active immunization

Figure 6. Schematic illustration of the activated NLRP3 inflammasome and the therapeutic effects of MCC950 in anti-NMDAR encephalitis. Overactivated NLRP3 inflammasome and inflammatory response were detected in anti-NMDAR encephalitis mice model induced by active immunization, companied with the overactivation of microglia. MCC950 had the potential protective effect to inhibit NLRP3 associated inflammatory cascade and alleviate the cognitive deficits in anti-NMDAR encephalitis mice model. NLRP3, the nucleotide-binding oligomerization domain like receptor family pyrin domain-containing 3; ASC, Apoptosis-associated speck-like protein containing a CARD; NEA, anti-NMDAR encephalitis mice model induced by active immunization; IL1β, interleukin 1β; IL18, interleukin 18. [Display omitted] •Cognitive dysfunction was found in the anti-NMDAR encephalitis mice model induced by active immunization with peptide GluN1356–385.•Overactivated NLRP3 inflammasome were firstly uncovered in the anti-NMDAR encephalitis mice model, leading to microglia overactivation and inflammatory cascade reaction.•MCC950, a specific inhibitor of the NLRP3 inflammasome, alleviated the inflammatory response and cognitive dysfunction in the anti-NMDAR encephalitis mice. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neurological disorder, characterized by cognitive deficits as one of its vital features. The nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome is a key contributor to neuroinflammation and cognitive deficits in neurological diseases. However, the underlying mechanism of anti-NMDAR encephalitis remains unclear, and the biological function of the NLRP3 inflammasome in this condition has not been elucidated. In this study, a mouse model of anti-NMDAR encephalitis was induced by active immunization with the GluN1356–385 peptide (NEA model). The NLRP3 inflammasome in the hippocampus and temporal cortex was investigated using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence staining. The impact of MCC950 on cognitive function and NLRP3 inflammation was assessed. Confocal immunofluorescence staining and Sholl analysis were employed to examine the function and morphology of microglia. In the current study, we discovered overactivation of the NLRP3 inflammasome and an enhanced inflammatory response in the NEA model, particularly in the hippocampus and temporal cortex. Furthermore, significant cognitive dysfunction was obs