Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

摘要: Histamine is an amine widely known as a peripheral inflammatory mediator and neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts innate modulator of microglial activity. Herein, we aimed to disclose role phagocytic activity reactive oxygen species (ROS) production explore consequences histamine-induced neuroinflammation dopaminergic (DA) neuronal survival. The effect on phagocytosis was assessed both vitro by using murine N9 cell line primary cultures vivo. Cells were exposed IgG-opsonized latex beads or phosphatidylserine (PS) liposomes evaluate Fcγ PS receptor-mediated phagocytosis, respectively. ROS protein levels NADPH oxidases Rac1 measure oxidative stress. DA survival evaluated vivo counting number tyrosine hydroxylase-positive neurons substantia nigra (SN) mice. We found triggers via receptor 1 (H1R) activation H1R H4R activation. By apocynin, broad oxidase (Nox) inhibitor, Nox1 knockout mice, signaling pathway involved induced vitro. Interestingly, apocynin annexin V (used inhibitor PS-induced phagocytosis) fully abolished neurotoxicity injection SN adult mice Blockade protected against expression death Overall, our results highlight relevance modulation ultimately may interfere with context Parkinson’s disease (PD) and, eventually, other neurodegenerative diseases which are accompanied microglia-induced neuroinflammation. Importantly, also open promising new perspectives for therapeutic use antagonists treat ameliorate processes.