Fig. 6.

ADP355 preserves markers of cerebrovascular integrity, synaptic density, and modulates reactive gliosis in PI-treated mice. Male C57BL/6 mice were treated daily with vehicle or lopinavir/ritonavir (150/ 37.5 mg/kg body weight) for 28 days, after which markers of cerebrovascular integrity, synaptic density, and reactive gliosis were evaluated in tissue homogenates prepared from the frontal cortex as described in Methods. Data depict mean ± SEM expression in lopinavir/ritonavir-treated mice presented as % vehicle (100 % line) on graph. Data were obtained from 12–20 mice/group, and were analyzed by 1-way ANOVA. a Expression of the tight junction proteins claudin-5, ZO-1, and occludin; and the matrix metalloproteinases MMP2 and MMP9. * and ** indicate significant (p<0.05 and 0.01, respectively) changes in expression in lopinavir/ritonavir/PBS-treated mice as compared to vehicle, while # and ## depict significant (p<0.05, p<0.01, respectively) changes in expression in lopinavir/ritonavir-treated mice given ADP355 as compared to lopinavir/ritonavir-treated given PBS. b Expression of the post-synaptic marker synapse associated protein 97 (SAP97), the pre-synaptic protein synapsin 1, and phosphorylated synapsin 1. *** indicates significant (p<0.001) the significant decrease in phosphorylated synapsin 1 expression in lopinavir/ritonavir/PBS-treated mice relative to vehicle mice, while # depicts the significant (p<0.05) reversal in phosphorylated synapsin 1 expression in lopinavir/ritonavir-treated mice given ADP355. c Expression of the glial markers GFAP and Iba-1. * indicates significant (p<0.05) increases in GFAP and Iba-1 expression in lopinavir/ritonavir-treated mice relative to vehicle-treated mice, while # depicts the significant (p<0.05) reversal in Iba-1 expression in lopinavir/ritonavir-treated mice given ADP355