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

ABSTRACT

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.