MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration

NLRP3 deficiency attenuates motor dysfunctions and dopaminergic neuronal loss in MPTP-treated mice. a–c Nlrp3+/+ or Nlrp3？/？ mice were administered with PBS or MPTP (40？mg/kg) for 5 days and then examined for motor activity impairment as described in the Methods. a The latent time to hold the bar in the string test 24？h post the final PBS or MPTP administration (Nlrp3+/+ mice, PBS (n？=？6), MPTP (n？=？10); Nlrp3？/？ mice, PBS (n？=？6), MPTP (n？=？11)). b The latent time to hold the bar in the catalepsy test 1？h post the final PBS or MPTP administration. (PBS (n？=？6), MPTP (n？=？11)). c The severity of hindlimb clasping in PBS- (n？=？6) or MPTP-treated (n？=？11) mice 1？h post the final PBS or MPTP administration. d Representative immunofluorescence image of the fixed brain sections containing SN of PBS- or MPTP-treated Nlrp3+/+ or Nlrp3？/？ mice after staining with anti-TH antibody (green). DAPI represents the nuclear signal (blue). Scale bars, 200？μm. e Quantification of relative TH-positive cells per DAPI in confocal images of PBS- or MPTP-treated Nlrp3 +/+ or Nlrp3？/？ mice (n？=？4). f Quantification of striatal dopamine levels of PBS- or MPTP-treated Nlrp3+/+ or Nlrp3？/？ mice as determined by HPLC-MS/MS (Nlrp3+/+ mice, PBS (n？=？11), MPTP (n？=？11); Nlrp3？/？ mice, PBS (n？=？11), MPTP (n？=？10)). Data were expressed as the mean？±？SEM. Asterisks indicate significant differences (*P？<？0.05, **P？<？0.01, ***P？<？0.001