Abstract
Periventricular white matter injury (PWMI) is very common in survivors of premature birth, and the final outcomes are a reduction in myelinated neurons leading to white matter hypomyelination. How and (or) why the oligodendrocyte lineage develops abnormally and myelination is reduced is a hot topic in the field. This study focuses on the effect of intrauterine inflammation on the proliferation of oligodendrocyte lineage cells and the underlying mechanisms. Lipopolysaccharide (LPS) (300 μg/kg) was intraperitoneally injected into pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish a rat model of intrauterine infection-induced white matter injury. Corpus callosum tissues were collected at postnatal day 14 (P14) to quantify the number of oligodendrocytes, the number and proliferation of oligodendrocyte precursor cells (OPCs), and the expression of myelin proteins (MBP and PLP). Furthermore, the expression of Wnt and Notch signaling-related proteins was analyzed. The results showed that the number of oligodendrocytes in the corpus callosum tissues of LPS-treated rats was reduced, and the expression levels of myelinating proteins were down-regulated. Further analysis showed that the Notch signaling pathway was down-regulated in the LPStreated group. These results indicate that intrauterine LPS may inhibit the proliferation of OPCs by down-regulating the Notch rather than the Wnt signaling pathway, leading to hypomyelination of white matter.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Araujo Júnior E, Carvalho FH, Tonni G, et al. Prenatal imaging findings in fetal Zika virus infection. Curr Opin Obstet Gynecol, 2017,29(2):95–105
Saliba E, Marret S. Cerebral white matter damage in the preterm infant: pathophysiology and risk factors. Semin Neonatol, 2001,6(2):121–133
Simonsen KA, Anderson-Berry AL, Delair SF, et al. Early-onset neonatal sepsis. Clin Microbiol Rev, 2014,27(1):21–47
Graf AE, Haines KM, Pierson CR, et al. Perinatal inflammation results in decreased oligodendrocyte numbers in adulthood. Life Sci, 2014,94(2):164–171
Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res, 2001,50(5):553–562
Leviton A, Paneth N. White matter damage in preterm newborns—An epidemiologic perspective. Early Hum Dev, 1990,24(1):1–22
Wakabayashi A, Sawada K, Nakayama M, et al. Targeting interleukin-6 receptor inhibits preterm delivery induced by inflammation. Mol Hum Reprod, 2013,19(11):718–726
Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology, 2011,99(3):177–187
Back SA, Riddle A, Dean J, et al. The instrumented fetal sheep as a model of cerebral white matter injury in the premature infant. Neurotherapeutics, 2012,9(2):359–370
Jin SJ, Liu Y, Deng SH, et al. Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury. J Huazhong Univ Sci Technolog Med Sci, 2015,35(6):904–909
Jin SJ, Liu Y, Deng SH, et al. Neuroprotective effects of activated protein C on intrauterine inflammationinduced neonatal white matter injury are associated with the downregulation of fibrinogen-like protein 2/fibroleukin prothrombinase and the inhibition of proinflammatory cytokine expression. Int J Mol Med, 2015,35(5):1199–1212
Dugas JC, Cuellar TL, Scholze A, et al. Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron, 2015,65(5): 597–611
Bialas AR, Stevens B. TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat Neurosci, 2013,16(12),1773–1782
Giera S, Deng Y, Luo R, et al. The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. Nat Commun, 2015,6:6121
Tsimis ME, Johnson CT, Raghunathan RS, et al. Risk factors for periventricular white matter injury in very low birthweight neonates. Am J Obstet Gynecol, 2016,214(3):380. e1–6
Van Well GTJ, Daalderop LA, Wolfs T, et al. Human perinatal immunity in physiological conditions and during infection. Mol Cell Pediatr, 2017,4(1):4
Peng CC, Chang JH, Lin HY, et al. Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis. Pediatr Neonatol, 2018,59(3):231–237
Deng Y, Xie D, Fang M, et al. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain. PLoS One, 2014,9(1):e87420
Zhang Z, Jyoti A, Balakrishnan B, et al. Trajectory of inflammatory and microglial activation markers in the postnatal rabbit brain following intrauterine endotoxin exposure. Neurobiol Dis, 2017,111:153–162
Lin W, Lin Y. Interferon-γ inhibits central nervous system myelination through both STAT1-dependent and STAT1-independent pathways. J Neurosci Res, 2010,88(12):2569–2577
Hossain S, Bhowmick S, Jahan S, et al. Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats. Neurotoxicology, 2016,56:150–158
French HM, Reid M, Mamontov P, et al. Oxidative stress disrupts oligodendrocyte maturation. J Neurosci Res, 2009,87(14):3076–3087
Kempuraj D, Selvakumar GP, Zaheer S, et al. Cross-talk between glia, neurons and mast cells in neuroinflammation associated with parkinson's disease. J Neuroimmune Pharmacol, 2018,13(1):100–112
Diaz A, Merino P, Manrique LG, et al. A cross talk between neuronal urokinase-type plasminogen qctivator (uPA) and astrocytic uPA receptor (uPAR) promotes astrocytic activation and synaptic recovery in the ischemic brain. J Neurosci, 2017,37(43):10 310–10 322
Fancy SP, Harrington EP, Baranzini SE, et al. Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer. Nat Neurosci, 2014,17(4):506–512
Chen HL, Chew LJ, Packer RJ, et al. Modulation of the Wnt/beta-catenin pathway in human oligodendroglioma cells by Sox17 regulates proliferation and differentiation. Cancer Lett, 2013,335(2):361–371
Aguirre A, Rubio ME, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature, 2010,467(7313):323–327
Author information
Authors and Affiliations
Corresponding author
Additional information
This project was supported by grants from Natural Science Foundation of China, Hubei Province (No. 2017CFB645) and National Natural Science Foundation of China (No. 81471519).
Rights and permissions
About this article
Cite this article
Ying, Yq., Yan, Xq., Jin, Sj. et al. Inhibitory Effect of LPS on the Proliferation of Oligodendrocyte Precursor Cells through the Notch Signaling Pathway in Intrauterine Infection-induced Rats. CURR MED SCI 38, 840–846 (2018). https://doi.org/10.1007/s11596-018-1951-9
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-018-1951-9