Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0087420
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dc.titleAstrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain
dc.contributor.authorDeng Y.
dc.contributor.authorXie D.
dc.contributor.authorFang M.
dc.contributor.authorZhu G.
dc.contributor.authorChen C.
dc.contributor.authorZeng H.
dc.contributor.authorLu J.
dc.contributor.authorCharanjit K.
dc.date.accessioned2020-03-26T06:44:22Z
dc.date.available2020-03-26T06:44:22Z
dc.date.issued2014
dc.identifier.citationDeng Y., Xie D., Fang M., Zhu G., Chen C., Zeng H., Lu J., Charanjit K. (2014). Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain. PLoS ONE 9 (1) : e87420. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0087420
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165961
dc.description.abstractHypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD), a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL) loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-? and IL-1? was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM) and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-? and IL-1? in primary cultured astrocytes as well as their corresponding receptors in primary culture APC + oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-? and IL-1?, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats. © 2014 Deng et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectinterleukin 1 receptor type I
dc.subjectinterleukin 1beta
dc.subjecttumor necrosis factor alpha
dc.subjecttumor necrosis factor receptor 1
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantigen presenting cell
dc.subjectapoptosis
dc.subjectarticle
dc.subjectastrocyte
dc.subjectbrain hypoxia
dc.subjectcell culture
dc.subjectcontrolled study
dc.subjectdemyelination
dc.subjectelectron microscopy
dc.subjectfemale
dc.subjecthypomyelination
dc.subjectimmunofluorescence
dc.subjectimmunopathogenesis
dc.subjectmyelination
dc.subjectnerve fiber
dc.subjectnonhuman
dc.subjectoligodendroglia
dc.subjectperiventricular white matter disorder
dc.subjectprotein expression
dc.subjectreal time polymerase chain reaction
dc.subjectupregulation
dc.subjectWestern blotting
dc.subjectwhite matter lesion
dc.subjectWistar rat
dc.subjectAnimals
dc.subjectAnimals, Newborn
dc.subjectApoptosis
dc.subjectAstrocytes
dc.subjectCell Hypoxia
dc.subjectCells, Cultured
dc.subjectCerebral Cortex
dc.subjectDemyelinating Diseases
dc.subjectHypoxia, Brain
dc.subjectInflammation Mediators
dc.subjectInterleukin-1beta
dc.subjectMyelin Sheath
dc.subjectOligodendroglia
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectTumor Necrosis Factor-alpha
dc.subjectUp-Regulation
dc.typeArticle
dc.contributor.departmentDEPT OF ANATOMY
dc.description.doi10.1371/journal.pone.0087420
dc.description.sourcetitlePLoS ONE
dc.description.volume9
dc.description.issue1
dc.description.pagee87420
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