Therapeutic effect of nicotine on neuroinflammation in mice and its mechanism
nicotine on Poly(I∶C)-induced neuroinflammation and cognitive behavioral changes in mice.Objective To investigate the therapeutic effect of α7-nicotinic acetylcholine receptor(α7nAchR)agonist Methods Sixty female C57BL/6J mice were randomly divided into the normal control group,Poly(I∶C)group,nicotine group and α7nAchR an-tagonist group(MLA group),with 15 mice in each group.Mice in the model group were given Poly(I∶C)12 mg/kgth-rough intraperitoneal injection to prepare the central nervous inflammation models.Mice in the nicotine group were intraper-itoneally injected with 1 mg/kg nicotine 30 min before injection of Poly(I∶C).Mice in the MLA group were intraperitone-ally injected with 5 mg/kg MLA 1 h before injection of Poly(I∶C)and 1 mg/kg nicotine 30 min before injection of Poly(I∶C).Mice in the model group and the normal control group were injected with the same amount of normal saline at the same time point.Three hours after modeling,6 mice in each group were randomly selected for water maze experiment and open field experiment.The times of crossing the original platform,escape latency,average movement speed and distance of mice were recorded,so as to evaluate the spatial learning and memory ability and autonomous motor ability of mice.Three mice in each group were randomly selected to be killed,and brain tissues were collected.The activation of microglia in hippocampus and prefrontal cortex was observed by immunohistochemical method to evaluate the degree of central ner-vous inflammation in mice.The mRNA levels of IL-6,TNF-α,INF-β,INF-α and IL-1β were detected by qPCR,and the protein phosphorylation level of NF-κB p65 was detected by Western blotting.Results Compared with the normal con-trol group,water maze test in the Poly(I∶C)group showed prolonged latency and reduced frequency of crossing the plat-form;open field test showed decreased mean motion speed and distance,increased activation of microglia in hippocampus and prefrontal lobe,increased expression levels of IL-6,TNF-α,INF-β,INF-α and IL-1β in the brain tissues,and in-creased level of NF-κB p65 phosphorylation in brain tissues(all P<0.05).Compared with the Poly(I∶C)group,the wa-ter maze test in the nicotine group showed prolonged latency and increased frequency of crossing the platform,the open field test showed increased mean movement speed and distance,decreased activation of microglia in hippocampus and pre-frontal lobe,and decreased expression levels of IL-6,TNF-α,INF-β,INF-α and IL-1β in the brain tissues,and de-creased level of NF-κB p65 phosphorylation in brain(all P<0.05).Compared with the nicotine group,the water maze test in the MLA group showed prolonged latency and decreased frequency of crossing the platform,the open field test showed decreased mean motion speed and distance,increased activation of microglia in hippocampus and prefrontal lobe,and in-creased expression levels of IL-6,TNF-α,INF-β,INF-α and IL-1β in the brain tissues,and increased level of NF-κB p65 phosphorylation in the brain tissues(all P<0.05).Conclusion Nicotine can improve the neuroinflammation and cognitive behavioral changes induced by Poly(I∶C)in mice,and the mechanism is related to the reduction of NF-κB p65 phosphorylation through nicotine acting on α7nAchR,thus reducing the release of inflammatory factors.
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