
Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats
Chen Guangxue, Chen Wujuan, Wang Lu, Zheng Xiuli
Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats
Objective To investigate the influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats. Methods A total of 24 rats pregnant for 18 days were randomly divided into control group and model group,with 12 rats in each group. The method of water platform sleep deprivation was used to establish a model of sleep deprivation; the rats in the model group received sleep deprivation for 72 hours,while those in the control group was fed normally without sleep deprivation. After modeling,6 pregnant rats were randomly selected from each group for ether anesthesia,and blood samples were collected from the abdominal aorta;brain tissue was completely removed,and stripping of fetal rats and placenta were performed. The remaining 6 rats in each group were subject to natural labor and normal feeding. Behavioral tests of the young rats were performed on days 34 and 64 days after birth;HE staining was used to observe the histomorphology of placenta,and immunofluorescent staining was used to observe the morphology of microglial cells and the proliferation of neurons in the hippocampus of fetal rats;high-performance liquid chromatography was used to measure the levels of tryptophan,kynurenine,and kynurenic acid (KYNA);the levels of plasma corticosterone and cytokines in placental tissue were measured for maternal rats. Results There were significant differences between the control group and the model group in total activity distance of the open field test on day 64,the time spent in the central area on day 34,and activity distance in the central area on day 64(P<0.05),and compared with the control group,the model group had a significant increase in the time of entering the open arm(P<0.05) and a significant reduction in the time of entering the closed arm(P<0.05) in the elevated plus maze test on day 34,as well as a significant increase in immobility time in the forced swimming test on day 64(P<0.05). The control group had a clear structure of the placenta and normal cell morphology,while the model group had shrinkage of some trophoblasts in the placenta,with a reticular structure,and a reduction in blood sinuses. Compared with the control group,the model group had significant reductions in the proliferation and processes of hippocampal neurons(P<0.05) and significant increases in the number of microglial cells(P<0.05),cell surface area(P<0.05),the levels of tryptophan,kynurenine,KYNA,interleukin-1β,interleukin-6,and tumor necrosis factor-α in the placenta,and the levels of KYNA in fetal brain tissue and corticosterone in the plasma of maternal rats (P<0.05). Conclusion Sleep deprivation in late pregnancy may induce placental inflammation in pregnant rats through the kynurenine pathway and affect the cognitive function of young rats.
late pregnancy / sleep deprivation / inflammation / kynurenine pathway / cognitive function
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