Fig. 1
From: The pentose phosphate pathway regulates chronic neuroinflammation and dopaminergic neurodegeneration
Increased expression and activity of the PPP in multiple PD models. a One year after an intraperitoneal injection of 5 mg/kg LPS, mouse midbrains displayed increased expression of G6PD, gp91phox, and Iba1 and decreased expression of TH. b The ratio of densitometry values of these proteins in a was analyzed and normalized to each responsive control. c The mRNA level of G6PD in the midbrain of mice with an intraperitoneal injection of saline or 5 mg/kg LPS. d Double-labeled immunofluorescence of G6PD (red) with microglial marker CD11b, astroglial marker GFAP, DA neuron maker TH, or neuronal marker Neu-N (green) in mouse SN displayed dramatic G6PD upregulation in microglia at 2 weeks after an intranigral injection of 2 μg LPS. Enlarged inserts in the top panel showed increased G6PD staining in microglia. e, f At 3 or 7 months after daily subcutaneous injection of MPTP (15 mg/kg for 6 days), mouse midbrains exhibited increased expression of G6PD, gp91phox, and Iba1 and reduced levels of TH. g One-year-old A53T α-synuclein transgenic mice revealed upregulation of G6PD and gp91phox in midbrains compared with age-matched wild-type mice. h Double-labeled immunofluorescence of G6PD (red) with CD11b, GFAP, or Neu-N (green) in neuron-glia cultures treated with LPS (10 ng/mL) for 48 h showed occurrence of LPS-induced upregulation of G6PD in activated microglia but not neurons or astroglia. Double-stained images of G6PD and CD11b in vehicle-treated control cultures, neurons, or astroglia, which were negative for CD11b staining and positive for DAPI staining, showed weak G6PD staining. i Increased expression of G6PD and Iba1 in microglia-enriched cultures upon LPS treatment for 24 h. j, k Rat mesencephalic neuron-glia cultures treated with LPS showed high activity of G6PD (j) and increased production of NADPH (k) compared with vehicle-treated cultures. All images are representative of three independent experiments. Results are the mean ± SEM of three independent experiments (b, c, f, g, i–k). *p < 0.05 and **p < 0.01 compared with vehicle-treated controls (b, c, f, i–k). *p < 0.05 compared with wild-type littermates (g)