丰富环境通过抑制NOD样受体蛋白3炎性小体活化缓解脂多糖小鼠的认知障碍

目的探讨丰富环境(EE)对脂多糖(LPS)诱导的小鼠认知功能障碍的影响及其可能机制。方法36只3周龄昆明小鼠进行8周的EE刺激或者标准环境(SE)饲养后分为以下3组:标准环境+生理盐水(SE+NS)组、标准环境+脂多糖(SE+LPS)组及丰富环境+脂多糖(EE+LPS)组。采用旷场实验检测小鼠的活动度;新旧事物识别实验检测小鼠认知功能;免疫组织化学方法检测小胶质细胞标记物离子钙接头蛋白分子1(IBA1)表达;Western blotting方法检测海马组织小胶质细胞激活标记物CD68及NOD样受体蛋白3(NOD-like receptor protein3,NLRP3)炎性小体相关蛋白的表达。结果旷场实验中,各组小鼠穿越的总格数无明显差异。在新旧事物识别实验中,与SE+NS组相比,SE+LPS组新事物辨别指数明显下降(P<0.05);与SE+NS组相比,小胶质细胞标记物IBA1表达上调(P<0.05);SE+LPS组海马CD68及NLRP3炎性小体相关蛋白的表达明显上调(P<0.05);而丰富环境可以逆转上述改变(P<0.05)。结论丰富环境可缓解脂多糖诱导的认知功能损伤,其机制可能与抑制海马小胶质细胞激活及NLRP3炎性小体的产生有关。

Environmental enrichment ameliorates lipopolysaccharide-induced cognitive impairment by inhibiting NOD-like recepter protein 3 in fla mmasome activation in mice

Objective To investigate the effect of environmental enrichment (EE) on lipopolysaccharide (LPS) induced cognitive dysfunction in mice.Methods A total of thirty six 3 weeks old Kunming mice experienced 8 weeks of EE or standard environment (SE) feeding. After 8 weeks, they were divided into three groups: standard environment+normal saline (SE+NS) group, standard environment+lipopolysaccharide (SE+LPS) group, environmental enrichment+lipopolysaccharide (EE+LPS) group. The open field test was used to measure the locomotive of mice, and the cognitive function was determined by novelty object recognition test. The expression of microglial marker ionized calcium binding adaptor molecule-1 (IBA-1) in hippocampus was determined by immunohistochemical staining. The expression of microglial activation marker CD68 and NOD-like receptor protein 3 (NLRP3) inflammasome related protein in the hippocampus was detected by Western blotting.Results In the open field test, there was no difference in the activity among the three groups. Compared with the SE＋NS group, SE＋LPS group showed decreased discrimination ratio in novelty object recognition task, with remarkably up-regulated expression of CD68 in the hippocampus (P<0.01). In addition, SE＋LPS group exhibited significantly enhanced expression of NLRP3, apoptosis associated speck-like protein (ASC), Caspase-1 and interleukin-1β(IL-1β) in the hippocampus compared with SE＋NS group (P<0.05). Compared with the SE＋LPS group, EE＋LPS group showed enhanced discrimination ratio in the object recognition task, with down-regulated expression of CD68, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the hippocampus (P<0.01).Conclusion Environmental enrichment can alleviate LPS induced cognitive dysfunction, which might be attributed to the inhibiting of microglia and NLRP3 activation in the hippocampus.