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

doi:10.13406/j.cnki.cyxb.003605

您当前的位置：

首页 >

文章列表页 >

Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats

Basic research | 更新时间：2025-10-23

- Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats
- Journal of Chongqing Medical University Vol. 49, Issue 10, Pages: 1095-1101(2024)
- 作者机构：
  
  1.首都医科大学附属北京积水潭医院，北京 102208
  2.中山大学附属第五医院妇产科，珠海 519000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003605
  CLC： R715.3;R748
- Received：28 June 2023，
  
  Revised：2024-04-01，
  
  Accepted：07 April 2024，
  
  Published：28 October 2024
- 稿件说明：
移动端阅览
陈光雪,陈武娟,王璐,等.孕晚期睡眠剥夺对孕鼠胎盘炎症、犬尿氨酸途径及幼鼠认知功能的影响[J].重庆医科大学学报,2024,49(10):1095-1101.

Chen Guangxue,Chen Wujuan,Wang Lu,et al.Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats[J].Journal of Chongqing Medical University,2024,49(10):1095-1101.
陈光雪,陈武娟,王璐,等.孕晚期睡眠剥夺对孕鼠胎盘炎症、犬尿氨酸途径及幼鼠认知功能的影响[J].重庆医科大学学报,2024,49(10):1095-1101. DOI： 10.13406/j.cnki.cyxb.003605.

Chen Guangxue,Chen Wujuan,Wang Lu,et al.Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats[J].Journal of Chongqing Medical University,2024,49(10):1095-1101. DOI： 10.13406/j.cnki.cyxb.003605.

摘要

目的

探究孕晚期睡眠剥夺对孕鼠胎盘炎症、犬尿氨酸途径及幼鼠认知功能的影响。

方法

24只孕18 d大鼠随机分为对照组和模型组，每组12只。水平台睡眠剥夺法建立睡眠剥夺模型，模型组接受为期72 h的睡眠剥夺，对照组不进行睡眠剥夺，正常饲养。建模完成后，对照组与模型组随机取6只孕鼠乙醚麻醉，腹主动脉采血，完整取出脑组织，剥离胎鼠、胎盘，其余6只自然分娩，正常饲养。于幼鼠出生后34 d、64 d进行行为学检测，苏木精-伊红（hematoxylin eosin，HE）染色观察胎盘组织形态，免疫荧光染色观察胎鼠海马小胶质细胞形态和神经元增殖情况。高效液相色谱法检测色氨酸、犬尿氨酸、犬尿喹啉酸（kynurenic acid，KYNA）水平。测定母鼠血浆皮质酮与胎盘组织细胞因子水平。

结果

与对照组相比，模型组幼鼠64 d旷场实验活动总距离、34 d中央区域停留时间、64 d中央区域活动距离存在差异（

0.05），34 d高架十字迷宫实验幼鼠进入开放臂的时间增多（

0.05），进入闭合臂的时间减少（

0.05），64 d强迫游泳实验幼鼠不动时间增加（

0.05）。对照组胎盘结构清晰，细胞形态正常，模型组胎盘部分滋养细胞皱缩，呈空网状，血窦减少。与对照组相比，模型组胎鼠海马神经元增殖、突起数量减少（

0.05），小胶质细胞数量增多（

0.05），细胞表面积增大（

0.05），胎盘色氨酸、犬尿氨酸、KYNA、白细胞介素-1β（interleukin-1β，IL-1β）、白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、胎鼠脑组织KYNA、母鼠血浆皮质酮水平升高（

0.05）。

结论

孕晚期睡眠剥夺可能通过犬尿氨酸途径引发孕鼠胎盘炎症反应，影响幼鼠认知功能。

Abstract

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（

0.05），and compared with the control group，the model group had a significant increase in the time of entering the open arm（

0.05） and a significant reduction in the time of entering the closed arm（

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（

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（

0.05） and significant increases in the number of microglial cells（

0.05），cell surface area（

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 （

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.

关键词

Keywords

references

Wang Z ， Chen WH ， Li SX ， et al . Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation [J ] . Mol Psychiatry ， 2021 ， 26 （ 11 ）： 6277 - 6292 ．

Wei R ， Duan XY ， Guo LX . Effects of sleep deprivation on coronary heart disease [J ] . Korean J Physiol Pharmacol ， 2022 ， 26 （ 5 ）： 297 - 305 ．

Ishkova A ， Wilson DL ， Howard ME ， et al . The effect of body position on maternal cardiovascular function during sleep and wakefulness in late pregnancy [J ] . J Matern Fetal Neonatal Med ， 2022 ， 35 （ 13 ）： 2545 - 2554 ．

Sonmezer E ， Özköslü MA ， Yosmaoğlu HB . The effects of clinical Pilates exercises on functional disability，pain，quality of life and lumbopelvic stabilization in pregnant women with low back pain：a randomized controlled study [J ] . J Back Musculoskelet Rehabil ， 2021 ， 34 （ 1 ）： 69 - 76 ．

DiPietro JA ， Watson H ， Raghunathan RS ， et al . Fetal neuromaturation in late gestation is affected by maternal sleep disordered breathing and sleep disruption in pregnant women with obesity [J ] . Int J Gynaecol Obstet ， 2022 ， 157 （ 1 ）： 181 - 187 ．

Nakahara K ， Michikawa T ， Morokuma S ， et al . Association of maternal sleep before and during pregnancy with sleep and developmental problems in 1-year-old infants [J ] . Sci Rep ， 2021 ， 11 （ 1 ）： 11834 ．

Khodaverdiloo A ， Farhadi M ， Jameie M ， et al . Neurogenesis in the rat neonate’s hippocampus with maternal short-term REM sleep deprivation restores by royal jelly treatment [J ] . Brain Behav ， 2021 ， 11 （ 12 ）： e2423 ．

Xie XT ， Ding DQ ， Bai DY ， et al . Melatonin biosynthesis pathways in nature and its production in engineered microorganisms [J ] . Synth Syst Biotechnol ， 2022 ， 7 （ 1 ）： 544 - 553 ．

Wang WQ ， Wang XY ， Liu L ， et al . Dietary tryptophan and the risk of obesity and type 2 diabetes：total effect and mediation effect of sleep duration [J ] . Obesity ， 2022 ， 30 （ 2 ）： 515 - 523 ．

Correia AS ， Vale N . Tryptophan metabolism in depression：a narrative review with a focus on serotonin and kynurenine pathways [J ] . Int J Mol Sci ， 2022 ， 23 （ 15 ）： 8493 ．

Martos D ， Tuka B ， Tanaka M ， et al . Memory enhancement with kynurenic acid and its mechanisms in neurotransmission [J ] . Biomedicines ， 2022 ， 10 （ 4 ）： 849 ．

Rentschler KM ， Baratta AM ， Ditty AL ， et al . Prenatal kynurenine elevation elicits sex-dependent changes in sleep and arousal during adulthood：implications for psychotic disorders [J ] . Schizophr Bull ， 2021 ， 47 （ 5 ）： 1320 - 1330 ．

Mithaiwala MN ， Santana-Coelho D ， Porter GA ， et al . Neuroinflammation and the kynurenine pathway in CNS disease：molecular mechanisms and therapeutic implications [J ] . Cells ， 2021 ， 10 （ 6 ）： 1548 ．

Dai DS ， Zheng BQ ， Yu ZG ， et al . Right stellate ganglion block improves learning and memory dysfunction and hippocampal injury in rats with sleep deprivation [J ] . BMC Anesthesiol ， 2021 ， 21 （ 1 ）： 272 ．

Salari N ， Darvishi N ， Khaledi-Paveh B ， et al . A systematic review and meta-analysis of prevalence of insomnia in the third trimester of pregnancy [J ] . BMC Pregnancy Childbirth ， 2021 ， 21 （ 1 ）： 284 ．

Tang YF ， Dai F ， Razali NS ， et al . Sleep quality and BMI in pregnancy- a prospective cohort study [J ] . BMC Pregnancy Childbirth ， 2022 ， 22 （ 1 ）： 72 ．

Yao ZY ， Li XH ， Zuo L ， et al . Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats [J ] . Zool Res ， 2022 ， 43 （ 3 ）： 380 - 390 ．

Lahimgarzadeh R ， Vaseghi S ， Nasehi M ， et al . Effect of multi-epitope derived from HIV-1 on REM sleep deprivation-induced spatial memory impairment with respect to the level of immune factors in mice [J ] . Iran J Basic Med Sci ， 2022 ， 25 （ 2 ）： 164 - 172 ．

Ehsanifar M ， Jafari AJ ， Montazeri Z ， et al . Learning and memory disorders related to hippocampal inflammation following exposure to air pollution [J ] . J Environ Health Sci Eng ， 2021 ， 19 （ 1 ）： 261 - 272 ．

Popova G ， Soliman SS ， Kim CN ， et al . Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids [J ] . Cell Stem Cell ， 2021 ， 28 （ 12 ）： 2153 - 2166 . e6．

Quarta A ， Berneman Z ， Ponsaerts P . Functional consequences of a close encounter between microglia and brain-infiltrating monocytes during CNS pathology and repair [J ] . J Leukoc Biol ， 2021 ， 110 （ 1 ）： 89 - 106 ．

Tang CF ， Wang CY ， Wang JH ， et al . Short-chain fatty acids ameliorate depressive-like behaviors of high fructose-fed mice by rescuing hippocampal neurogenesis decline and blood-brain barrier damage [J ] . Nutrients ， 2022 ， 14 （ 9 ）： 1882 ．

Zhao SJ ， Muyayalo KP ， Luo J ， et al . Next generation of immune checkpoint molecules in maternal-fetal immunity [J ] . Immunol Rev ， 2022 ， 308 （ 1 ）： 40 - 54 ．

Kwon HK ， Choi GB ， Huh JR . Maternal inflammation and its ramifications on fetal neurodevelopment [J ] . Trends Immunol ， 2022 ， 43 （ 3 ）： 230 - 244 ．

Karahoda R ， Robles M ， Marushka J ， et al . Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth [J ] . Hum Mol Genet ， 2021 ， 30 （ 22 ）： 2053 - 2067 ．

Broekhuizen M ， Jan Danser AHJ ， Reiss IKM ， et al . The function of the kynurenine pathway in the placenta：a novel pharmacotherapeutic target? [J ] . Int J Environ Res Public Health ， 2021 ， 18 （ 21 ）： 11545 ．

Milosavljevic S ， Smith AK ， Wright CJ ， et al . Kynurenine aminotransferase II inhibition promotes sleep and rescues impairments induced by neurodevelopmental insult [J ] . Transl Psychiatry ， 2023 ， 13 （ 1 ）： 106 ．

Savonije K ， Weaver DF . The role of tryptophan metabolism in Alzheimer’s disease [J ] . Brain Sci ， 2023 ， 13 （ 2 ）： 292 ．

Murakami Y ， Imamura Y ， Kasahara Y ， et al . Maternal inflammation with elevated kynurenine metabolites is related to the risk of abnormal brain development and behavioral changes in autism spectrum disorder [J ] . Cells ， 2023 ， 12 （ 7 ）： 1087 ．

Bai MY ， Lovejoy DB ， Guillemin GJ ， et al . Galantamine-memantine combination and kynurenine pathway enzyme inhibitors in the treatment of neuropsychiatric disorders [J ] . Complex Psychiatry ， 2021 ， 7 （ 1/2 ）： 19 - 33 ．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Physical exercise ameliorates cognitive impairment caused by sleep deprivation by modulating autophagy

Advances in the study of hippocampal subregion in Alzheimer's disease

Research progress of cognition, sleep and plasma biomarkers in patients with cerebral small vessel disease

On the relevance between cognitive function and stigma in patients with deficit schizophrenia

New advances in neuropsychological assessment: the relationship between cognitive function and brain amyloid deposition

Related Author

Guo Shan

Tang Ling

Shuyue Lü

Wenyue Sun

Fan Wu

Qing Zhao

Xiaohan Chen

Baofeng Gong

Related Institution

Department of Neurology，University-Town Hospital of Chongqing Medical University

Department of Neurology, South Lake, China-Japan Union Hospital of Jilin University, Jilin Provincial Engineering Laboratory of Memory and Cognitive Impairment Disease

Department of Neurology, Second Affiliated Hospital of Naval Medical University

Affiliated Psychological Hospital of Anhui Medical University

Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

⁰