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. 2026 Mar 28;12:121. doi: 10.1038/s41531-026-01319-6

Fig. 3. Inhibition of O-GlcNAcase by Thiamet G restores motor function, dopaminergic integrity, and attenuates neuroinflammation in an LPS-induced PD mouse model.

Fig. 3

The mice received bilateral injections of LPS (5 μg) into the SN of the brain to induce neuroinflammation. Thiamet G (ThiaG) was administered intraperitoneally at a dose of 20 mg/kg, three times per week for four weeks. Motor coordination and bradykinesia were assessed using the rotarod test (A) and pole test (B) at 4 weeks post-injection (n = 6 per group). C Western blot analysis of TH expression in SN tissue lysates. TH levels were normalized to β-actin (n = 3 per group). Dopaminergic neuronal loss was visualized via TH immunohistochemistry in the ST (D) and SN (E). Scale bars = 100 μm (n = 3 per group). Representative immunofluorescence images of SN sections stained for TH (green), GFAP (astrocyte marker, red; F), Iba1 (microglial marker, red; G), and DAPI (nuclear counterstain, blue). Scale bars = 50 μm (n = 3 per group). H Western blot analysis of pro-inflammatory enzymes iNOS and COX2 in SN tissue lysates. Expression levels were normalized to β-actin (n = 3 per group). I Western blot analysis of NF-κB signaling pathway proteins, including phosphorylated and total p65 and IκB. The levels of p-p65 and p-IκB were normalized to total p65 and IκB, respectively (n = 3 per group). J Western blot analysis of inflammasome components, including NLRP3, ASC, cleaved caspase-1, and total caspase-1. NLRP3 and ASC levels were normalized to β-actin, while cleaved caspase-1 was normalized to total caspase-1 (n = 3 per group). K Representative immunofluorescence images of SN tissue showing ASC (green), Iba1 (red), and DAPI (blue). Scale bar = 10 μm (n = 3 per group). L ELISA analysis of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, TGF-β) in SN tissue lysates (n = 3 per group). Data are presented as mean SEM; **p < 0.05, **p < 0.01, ***p < 0.001 versus control, #p < 0.05, ##p < 0.01, ###p < 0.001 versus LPS. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc multiple comparison test.