Fig. 9

IFNAR1KO limits activation of p38 MAPK in the cerebral cortex of HIVgp120tg mice, and inhibition of the active kinase is neuroprotective. The protein levels of phospho-p38 (phospho-p38) and p38 MAPK protein (p38) were measured by Western blot analysis in the cerebral cortex (a) and hippocampus (b). Densitometric quantification of p-p38 and p38 in the cortex (c) and in the hippocampus (d). e, f Mixed neuronal-glial cerebrocortical cell cultures from rat were grown on glass coverslips and exposed between DIV 17–23 for 24 h to gp120 of HIV-1 (200 pM) or the ERK kinase inhibitor PD98059 (01, 0.5, 1, or 2 μM) in the presence or absence of the p38 MAPK blocker SB203580 (1 μM). Representative samples are shown in e, neuronal MAP-2 (red), nuclear DNA (blue). Subsequently, neuronal survival was assessed as described in methods (f). Genotypes: WT (WT), HIVgp120tg (GP), IFNAR1KO (KO), and IFNAR1KO × gp120 (KOGP). Values are presented in combined box-dot plots with the 25th and 75th percentiles. The middle line of the box shows the median, and the mean is indicated by a “+”; ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05; ANOVA and Tukey’s HSD post hoc test; n.s., not significant; a–d, n = 9–10 of 11–14-month-old animals (each 4–5 males and 4–5 females) per group/genotype (total n = 37 animals). f, n = 2–6 independent experiments per condition; circles represent average neuronal survival observed per coverslip