Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia.
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.
Croslan
DaJoie R
DR
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Schoell
Matthew C
MC
Ford
Gregory D
GD
Pulliam
John V
JV
Gates
Alicia
A
Clement
Ceilessia M
CM
Harris
Adalynn E
AE
Ford
Byron D
BD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008954:Models, Biological; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020890:Neuregulin-1; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C490580:Nrg1 protein, rat