Fig. 6
From: The pentose phosphate pathway regulates chronic neuroinflammation and dopaminergic neurodegeneration
G6PD inhibition attenuated LPS-elicited oxidative stress, microglial activation, DA neurodegeneration, and locomotor deficit. C57BL/6 J mice received an intranigral injection of LPS (2 μg) with 6-AN (20 nmol) or saline. Six weeks later, oxidative stress (a, b), microglial activation (a, c–e, g, h), loss of DA neurons (a, c, f, g, i), and locomotor deficit (j) were determined by immunofluorescence (a, b), immunochemistry (c–f), Western blotting assay (g–i), and the rotarod behavior test (j). a, b Representative immunofluorescent images (a) and the quantification of 3-NT staining showed that injection of 6-AN mitigated LPS-induced oxidative stress in the SN (b, saline vs. LPS, *p = 0.0031; LPS vs. 6-AN + LPS, #p = 0.0026). c–e, g, h LPS-elicited nigral microglial activation, as shown by enhanced immunoreactivity of CD11b (d, saline vs. LPS, *p < 0.0001; LPS vs. 6-AN + LPS, #p = 0.009), morphological changes from ramified resting shape to activated appearance with enlarged and irregular cell body (e, Saline vs. LPS, *p = 0.0001; LPS vs. 6-AN + LPS, #p = 0.0032), the expression of Iba1 (h, saline vs. LPS, *p = 0.028; LPS vs. 6-AN + LPS, #p = 0.018) was dampened by 6-AN injection. c, f, g, i Injection of 6-AN protected DA neurons from LPS-elicited degeneration as shown by improvement in the integrity of TH-IR fibers, the number of TH-IR neurons (f, saline vs. LPS, *p = 0.0006; LPS vs. 6-AN + LPS, #p = 0.006) and the expression of TH (i, saline vs. LPS, *p = 0.016; LPS vs. 6-AN + LPS, #p = 0.037). j LPS-elicited impairment of locomotor activity of mice measured by the rotarod behavior test was rescued by 6-AN injection (j, saline vs. LPS, *p = 0.0006; LPS vs. 6-AN + LPS, #p = 0.005). Results are mean ± SEM (b, d–f, h–j). *p < 0.05 compared with vehicle-injected controls. #p < 0.05 compared with LPS-injected groups. Significance was determined by one-way ANOVA with Tukey’s multiple post hoc testing. Immunostaining images were representative of 5 to 11 mice. Numbers within the bars indicate the number of mice in each treatment group