Figure 7.

Gemfibrozil (Gem) protects the nigrostriatal pathway via astrocytic GDNF in the MPTP mouse model. A, Genotyping of Gdnf^Δastro (astrocyte-specific GDNF knock-out) mice. B, Nigral sections of 6- to 8-week-old Gfap^cre mice or Gdnf ^Δastro mice were double labeled for GDNF and GFAP. Results represent the analysis of two sections of each of three mice per group. The 6- to 8-week-old Gfap^cre mice (n = 6/group) or Gdnf ^Δastro mice (n = 6/group) were lesioned with MPTP (20 mg/kg body weight/injection, four intraperitoneal injections at every 2 h interval). At 4 h following the last MPTP injection, mice were fed gemfibrozil (7.5 mg/kg body weight/d) via oral gavage for 7 d. C, Representative TH immunostaining from both Gfap^cre (left) and Gdnf ^Δastro (right) mice. D, Stereological counting of nigral TH cells in Gfap^cre and Gdnf ^Δastro mice. A two-way ANOVA results in F_(2,30) = 197.4 > F_c = 3.31 (****p < 0.0001) for treatment and F_(1,30) = 13.77 > F_c = 4.17 for genotype. E–G, Representative immunoblots from the nigral lysate tissue from Gfap^cre (E) and Gdnf ^Δastro (F) mice and corresponding densitometric analyses (G). Results are the mean ± SEM of three independent immunoblots. A two-way ANOVA was adopted to identify significant differences between treatment and genotype and found F_(2,30) = 120.1 > F_c = 3.31 (****p < 0.0001) for treatment and F_(1,30) = 42.74 > F_c = 4.17 (****p < 0.0001) for genotype. H, I, Representative striatal TH staining from both Gfap^cre (top) and Gdnf ^Δastro (bottom) mice (H) and corresponding optical density measurements to quantify striatal TH fiber density (I). A two-way ANOVA found F_(2,30) = 157.5 > F_c = 3.31 for treatment and F_(1,30) = 28.03 > F_c = 4.17 (****p < 0.0001). Post hoc Sidak's multiple-comparison tests were used to identify significant differences among the control, MPTP, and MPTP + Gem groups (****p < 0.0001) and are represented on the figure.