Effect of OLIG1 on the development of oligodendrocytes and myelination in a neonatal rat PVL model induced by hypoxia-ischemia

摘要

OLIG1 is an oligodendrocyte (OL) transcription factor, which can contribute to the proliferation and differentiation of OLs, and the maturation of myelin. The aim of this study was to clarify the role of OLIG1 in neonatal Sprague Dawley rats with periventricular leukomalacia (PVL), induced by hypoxia-ischemia (HI). Newborn rats in the HI group were subjected to ligation of the right carotid artery, followed by 8% oxygen delivery for 2 h, while rats in the normoxia group were only subjected to isolation of the right carotid artery, without exposure to hypoxia. Samples of brain tissue from rats in both groups were collected at 1, 3, 7, 14 and 21 days. In the HI group, observation by transmission electron microscopy (TEM) revealed OLs with a damaged nuclear membrane, cellular atrophy, deformation and necrosis, and cells in myelin with a high number of small vacuoles. A double-label immunofluorescence assay revealed the translocation of OLIG1 from the cytoplasm to the nucleus, while western blot and reverse transcription-quantitative polymerase chain reaction assays showed that there is a significant decrease, followed by an increase, in the gene and protein expression levels of OLIG1 and myelin basic protein (MBP). Despite the increase at the late stages of HI, the final levels of these proteins remained lower than the corresponding levels in the normoxia group. In conclusion, the decreased protein expression of OLIG1 following HI plays an important role in inhibiting the development and maturation of OLs and myelin. Although OLIG1 may, via its nuclear translocation, promote the growth and development of myelin to a certain extent, this factor fails to fully repair injured myelin.