Histamine 2/3 receptor agonists alleviate perioperative neurocognitive disorders by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway in aged rats.
Abstract
Microglia, the principal sentinel immune cells of the central nervous system (CNS), play an extensively vital role in neuroinflammation and perioperative neurocognitive disorders (PND). Histamine, a potent mediator of inflammation, can both promote and prevent microglia-related neuroinflammation by activating different histamine receptors. Rat microglia express four histamine receptors (H1R, H2R, H3R, and H4R), among which the histamine 1 and 4 receptors can promote microglia activation, whereas the role and cellular mechanism of the histamine 2 and 3 receptors have not been elucidated. Therefore, we evaluated the effects and potential cellular mechanisms of histamine 2/3 receptors in microglia-mediated inflammation and PND. This study investigated the role of histamine 2/3 receptors in microglia-induced inflammation and PND both in vivo and in vitro. In the in vivo experiments, rats were injected with histamine 2/3 receptor agonists in the right lateral ventricle and were then subjected to exploratory laparotomy. In the in vitro experiments, primary microglia were pretreated with histamine 2/3 receptor agonists before stimulation with lipopolysaccharide (LPS). Cognitive function, microglia activation, proinflammatory cytokine ...Continue Reading
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Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation
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