Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia

• Published in: Brain research 2008-05, Vol.1210, p.39-47
• Main Authors: Croslan, DaJoie R, Schoell, Matthew C, Ford, Gregory D, Pulliam, John V, Gates, Alicia, Clement, Ceilessia M, Harris, Adalynn E, Ford, Byron D
• Format: Article
• Language: English
• Subjects: Acetylcholine receptor reducing activity; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Brain Infarction - drug therapy; Brain Infarction - metabolism; Brain Infarction - physiopathology; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Cytoprotection - drug effects; Cytoprotection - physiology; Enzyme Inhibitors - pharmacology; Glial growth factor; Glutamate excitotoxicity; Heregulin; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - physiopathology; Ischemia; Medical sciences; Models, Biological; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Nerve Tissue Proteins - pharmacology; Neu differentiation factor; Neuregulin; Neuregulin-1; Neurology; Neuronal cell culture; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; Oxygen glucose deprivation; Pharmacology. Drug treatments; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.02.059

Abstract We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation. When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival. NRG-1 administration also resulted in a significant decrease in annexin V, an early marker of apoptosis. However, the neurotoxic actions of glutamate were unaffected by NRG-1. The neuroprotective effects of NRG-1 were prevented by an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. These results provide a new model to gain insight into the mechanisms employed by NRG-1 to protect neurons from ischemic brain injury.