Activation of Dopamine D2 Receptor Alleviates Neuroinflammation and Neuronal Injury in Mice Model of Allergic Rhinitis With Olfactory Dysfunction

Background: Allergic rhinitis (AR) is a common chronic allergic disease of the upper airway that not only causes peripheral inflammation, but also induces neuroinflammation in the hippocampus, prefrontal cortex, olfactory bulb and other brain areas. Recent studies have suggested that the dopamine D2 receptor acts as a key target in regulating immune functions and neuroinflammatory reaction, which may be a promising target for AR-induced olfactory dysfunction (OD).Methods: An AR mouse model with OD induced by ovalbumin (OVA) were constructed. A coculture system of olfactory bulb neurons (OBNs) and microglias was established. The buried food pellet test was to evaluate the olfactory function of the mice. Immunofluorescence staining, HE staining, ELISA, Western blotting, and TUNEL staining were also used to investigate the molecular mechanisms underlying the anti-inflammatory effects of the dopamine D2 receptor in AR-induced OD.Results: We confirmed that AR mice with or without OD had the characteristics of AR, but the expression of the microglial marker CD11b and the related cytokines (TNF-α, IL-1β and IL-6) in the AR mice with OD were significantly increased in the olfactory bulb compared with those of mice without OD. Nasal administration of quinpirole, a dopamine D2 receptor agonist, shortened the time to find the food pellets, inhibited the expression of TLR4/MyD88/NF-κB signalings and the levels of TNF-α, IL-1β and IL-6. In the coculture system of OBNs and microglias, quinpirole inhibited the release of TLR4/MyD88/NF-κB signalings-dependent inflammatory cytokines in the microglias, which was accompanied by decreased AMPA receptor GluR1, increased GluR2 and reduced TUNEL positive cells in the OBNs.Conclusion: Activation of the dopamine D2 receptor inhibits the release of inflammatory cytokines through the microglia-dependent TLR4/MyD88/NF-κB signalings, alleviates AMPA receptor-mediated damage of the olfactory bulb, and protects olfactory function.