Neuroprotective Effects of Neuregulin-1 ß on Oligodendrocyte Type 2 Astrocyte Progenitors Following Oxygen and Glucose Deprivation

• Published in: Pediatric neurology Vol. 50; no. 4; pp. 357 - 362
• Main Authors: Linying, Zhou, PhD, Wei, Wang, PhD, Minxia, Wu, PhD, Wenmin, Zhang, PhD, Liangcheng, Zhang, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Astrocytes - drug effects; Astrocytes - physiology; Brain - drug effects; Brain - physiopathology; Cell Hypoxia - physiology; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Chromones - pharmacology; Enzyme Inhibitors - pharmacology; Glucose - deficiency; Glucose - metabolism; ischemia; Morpholines - pharmacology; Neural Stem Cells - drug effects; Neural Stem Cells - physiology; neuregulin; Neuregulin-1 - metabolism; Neurology; oligodendrocyte; Oligodendroglia - drug effects; Oligodendroglia - physiology; Oxygen - metabolism; oxygen glucose deprivation; Pediatrics; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats, Sprague-Dawley; Signal Transduction - drug effects; oxygen glucose deprivation; neuregulin; apoptosis; oligodendrocyte; ischemia
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2013.12.007

Abstract Background Hypoxic-ischemic brain injury in neonates, especially in premature infants, is one of the main contributors to the mortality of newborns and can cause nervous system dysfunction in children. The major pathogenesis seems to be cerebral ischemia/reperfusion in the immature white matter that preferentially targets vulnerable premyelinating oligodendrocytes. Objectives The goal of this study was to culture oligodendrocyte type 2 astrocyte cells in an oxygen and glucose deprivation environment to simulate ischemia injury and examine the cellular and molecular mechanisms involved in the neuroprotective effects of neuregulin-1ß on ischemia-induced immature oligodendrocytes. Methods Oligodendrocyte type 2 astrocyte cells were cultured from neonatal Sprague-Dawley rat cerebra. The cells were divided into two groups: one was subjected to oxygen and glucose deprivation for 9 hours and the other was treated with 50 ng/mL or 100 ng/mL neuregulin-1β during oxygen and glucose deprivation. Cell survival was determined by Trypan Blue staining and cell apoptosis were observed by fluorescein isothiocyanate-Annexin V and propidium iodide double staining. To study if the PI3K-Akt signaling pathway was involved in the mechanism of protective effect of neuregulin-1ß, Western blot analysis was used to quantitative the changes of protein. Results Treatment with neuregulin-1ß within the period of oxygen and glucose deprivation significantly increased cell survival and also resulted in a significant decrease in cell apoptosis. The neuroprotective effects of neuregulin-1ß were prevented by treatment with Ly294002, an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. Conclusions These results suggest that neuregulin-1ß could protect the oligodendrocyte type 2 astrocyte progenitors against hypoxic injury, and the mechanism may be associated with the PI3K-Akt signaling pathway.