Fig. 6

TNF-a synthesis in the cerebellum is TRADD/RIP1/TRAF2 complex formation-dependent. Analysis of TNF-a expression and NF-kB p50 subunit nuclear translocation was performed in slices incubated with R7050 as described in the “Material and methods” section. The expression of TNF-a was reduced in neurons (a, d), microglia (Iba-1: red; TNF-a: green; b, e) and astrocytes (GFAP: green; TNF-a: red; c, e) in hyperammonemic rats after 30 min of incubation with R7050. These effects were due to a reduction in the nuclear NF-kB p50 in Purkinje neurons (f, i), microglia (g, k), and astrocytes (h, l). R7050 treatment also restored the nucleolar translocation of the p50 subunit in Purkinje neurons (j). The values are the mean ± SEM of 4 rats per group. Values that were significantly different from those of the control rats are indicated by asterisks, and values that were significantly different from those of the HA VH rats are indicated by a. + refers to microglia expressing TNF-a in HA VH rats vs microglia expressing TNF-a in C VH rats, # refers to astrocytes expressing TNF-a in HA VH rats vs microglia expressing TNF-a in HA + R7050 rats, and @ refers to astrocytes expressing TNF-a in HA VH rats vs astrocytes expressing TNF-a in HA + R7050 rats. One symbol indicates p ≤ 0.05, two symbols indicate p < 0.01, three symbols indicate p ≤ 0.001, and four symbols indicate p < 0.0001. C VH = cerebellar slices obtained from vehicle-treated control rats, C + R7050 = cerebellar slices obtained from control rats and incubated with R7050, HA VH = cerebellar slices obtained from vehicle-treated hyperammonemic rats, HA + R7050 = cerebellar slices obtained from hyperammonemic rats and incubated with R7050