title: Administration of dexamethasone to neonatal rats induces hypomyelination and changes in the morphology of oligodendrocyte precursors.
abstract: To examine whether hypomyelination in neonatal rats might be related to apoptosis of oligodendrocyte progenitors, we administered dexamethasone (0.5 mg/kg SC) to neonatal rats on postnatal (P) days 1 through 5. Immunofluorescent staining and Western blotting for myelin basic protein (MBP) were performed on P14. Morphologic changes associated with apoptotic death of oligodendrocyte progenitors were assessed by using immunofluorescent staining on P5 of surface markers present at different developmental stages of oligodendrocyte progenitors (O4 and O1) and by double-staining with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end-labeling (TUNEL) and O4 or O1. Administration of dexamethasone to neonatal rats reduced the expression of MBP in the white matter by P14. In addition, dexamethasone reduced the expression of O4-positive cells, presumably preoligodendrocytes, in the corpus callosum and induced degenerative changes, such as cytoplasmic condensation and fragmented, tortuous processes, in oligodendrocyte progenitors, and increased the number of TUNEL-positive pyknotic nuclei of oligodendrocyte progenitors. These findings suggest that the dexamethasone-induced decreased expression of MBP in the cerebral hemispheres of the neonatal rats is due to apoptotic degeneration of oligodendrocyte progenitors. Administration of dexamethasone during the critical period of brain development may increase the risk of apoptosis in oligodendrocyte progenitors, subsequently resulting in hypomyelination.
authors.affiliation: Department of Nanobiomedical Science, WCU Research Center of Nanobiomedical Science, Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea.
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Young J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Young P
authors.initials: YP
authors.lastname: Chang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018709:Statistics, Nonparametric
chemical_list: D004676:Myelin Basic Protein; D003907:Dexamethasone
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