The relationship between inositol phosphatase-1 and cognitive impairment induced by hippocampal neuritis in intrauterine infected mice
10.3760/cma.j.issn.2095-428X.2018.11.014
- VernacularTitle:肌醇磷酸酶-1与宫内感染小鼠海马神经炎性反应引起认知障碍的关系
- Author:
Duoduo LI
1
;
Yuan CHENG
;
Zhenxiao LI
;
Fenglian ZHU
Author Information
1. 新乡医学院第一附属医院小儿内科三病区
- Keywords:
Intrauterine infection;
Inositol phosphatase-1;
Cognitive disorder
- From:
Chinese Journal of Applied Clinical Pediatrics
2018;33(11):850-853
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationship between cognitive impairment and SH2 domain-containing inositol phosphatase-1 (SHIP-1) induced by hippocampal neuritis in intrauterine infected mice.Methods Thirty C57BL/6 female mice and 15 male mice were caged in a ratio of 2 ∶ 1.After that,the pregnant mice were divided into 2 groups.A mice model of intrauterine infection was established that intrauterine infection group (lipopolysaccharides,LPS group) induced by LPS at the concentration of 350 μg/kg and control group treated with same volume of saline (9 g/L).At 3 days postpartum,15 mice in each group were killed for hippocampus,and the protein levels of SHIP-1,nuclear factor-κB(NF-κB) p65 and phosphorus NF-κB(NF-κBp) in the hippocampus of the newborn mice were detected by Western blott,while the levels of interleukin 1β (IL-1β) and tumor necrosis factor (TNF-α)were detected by using enzyme linked immunosoobent assay.When the remaining mice were 8 weeks old(10 in each group),Morris water maze experiments were performed respectively,which the mice were tested for evaluating learning and memory function by positioning navigation and space exploration experiments.Results The expression of SHIP-1 was significantly increased in control group (0.677 ± 0.074) compared with LPS group (0.317 ± 0.095,t =2.984,P =0.041),while the levels of NF-κB p65,and NF-κBp,were significantly lower in control group (0.630 ± 0.109,0.352 ± 0.084) than LPS group(0.630 ± 0.109,0.352 ± 0.084) (t =3.516,5.161,P =0.025,0.007).Moreover,LPS significantly enhanced the expression of IL-1β and TNF-α [(5.875 ± 0.349) pg/mg,(14.256 ± 0.784)pg/mg] compared with control group[(1.621 ± 0.151) pg/mg,(3.984 ± 0.255) pg/mg],and the differences were significant(t =11.190,12.460,P=0.000,0.000).By the average Escape Latency tests for6 days,LPS group [at 1-6 days (58.286±1.418) s,(56.036 ±2.252) s,(55.071 ±1.856) s,(50.071 ±3.251) s,(52.893 ±2.372) s,(46.929 ±3.761) s] markedly impaired the learning capacity compared with the control group[(53.679 ±2.413) s,(47.571 ±3.529) s,(54.071 ±2.777) s,(47.250 ±2.864) s,(45.107 ±3.447) s,(42.393 ±3.463) s],and the difference was significant (F =4.466,P =0.001).Concurrently,in probe trains LPS group increased the time of in zone southeast latency to first [(44.080 ± 6.313) s] compared with the control group [(25.900 ± 6.033) s],while shortened the period of in zone platform duration and in zone SE duration [(0.000 ± 0.040) s,(4.000 ± 1.693) s],decreased the times of in zone SE frequency and in zone platform frequency[(0.100 ±0.100) times,(1.000 ±0.394)times] compared with the control group [(0.400 ± 0.202) s,(14.360 ± 5.000) s,(0.600 ± 0.267) times,(3.400 ±0.763) times] (t=2.082,1.746,1.962,2.794,1.756,P=0.026,0.049,0.033,0.006,0.048).Conclusion The expression of SHIP-1 in hippocampus of newborn mice with intrauterine infection is decreased,and the inhibitory effect of SHIP-1 on the expression of downstream pro-inflammatory cytokines NF-κB,inflammatory cytokines IL-1β and TNF-α is decreased,along with cognitive impairments.
