Fig. 6

Histamine induces DA toxicity via H1R activation and involves oxidative stress and PS-mediated phagocytosis. a Bar graph depicts the percentage of TH+ cells in the SN of mice. A significant reduction in the number of TH+ neurons was found in 100 μM histamine (H100)-treated mice as compared with saline. Antagonist (Ant) for H1R abolished the toxicity induced by histamine. The toxic effect induced by histamine involves the production of ROS and PS-induced phagocytosis, since both apocynin (“Apo”, NADPH oxidase inhibitor) and annexin V (“AnxV”, blocker of PS residues) could inhibit dopaminergic toxicity. Data are expressed as mean ± SEM (n = 4–7 mice) and as a percentage of saline animals. *P < 0.05 and ***P < 0.001, using one-way ANOVA followed by Bonferroni’s multiple comparison test. b Representative immunostainings for TH in the SN of adult mice. A notable decrease in the number of TH+ cells could be observed in mice injected with histamine when compared with saline animals. c Bar graph depicts Nox1 protein expression levels in the SN. Increased expression of Nox1 protein found in histamine (H100)-treated mice was completely abolished by the H1R antagonist. Data are expressed as mean ± SEM (n = 4 mice). *P < 0.05 and **P < 0.01, using one-way ANOVA followed by Bonferroni’s multiple comparison test. d Representative Nox1 (65 kDa) and GAPDH (37 kDa) Western blots in the SN of adult mice in vivo. e Representative confocal photomicrographs showing that histamine-induced Nox1 expression in the perinuclear region of microglial cells in the SN in vivo. Cells were stained for CD11b (green), Nox1 (red), and Hoechst 33342 (nuclei in blue). White arrows highlight Nox1 staining in microglial cells. Scale bar 10 μm