Neuregulin-1β regulates outgrowth of neurites and migration of neurofilament 200 neurons from dorsal root ganglial explants in vitro

Neuregulin-1β (NRG-1β) signaling has multiple functions in neurons. To assess NRG-1β on neurite outgrowth and neuronal migration in vitro, organotypic dorsal root ganglion (DRG) neuronal culture model was established. Neurite outgrowth and neuronal migration were evaluated using this culture model in the presence (5nmol/L, 10nmol/L, 20nmol/L) or absence of NRG-1β. Neurofilament 200 (NF-200)-immunoreactive (IR) neurons were determined as the migrating neurons. The number of nerve fiber bundles extended from DRG explant increased significantly in the presence of NRG-1β (5nmol/L, 23.0±2.2, P<0.05; 10nmol/L, 27.0±2.7, P<0.001; 20nmol/L, 30.8±3.7, P<0.001) as compared with that in the absence of NRG-1β (19.0±2.2). The number of neurons migrating from DRG explants increased significantly in the presence of NRG-1β (5nmol/L, 39.6±5.0, P<0.05; 10nmol/L, 54.6±6.7, P<0.001; 20nmol/L, 62.2±5.7, P<0.001) as compared with that in the absence of NRG-1β (31.6±4.0). Moreover, the increase of the number of nerve fiber bundles and the number of migrating NF-200-IR neurons was dose-dependent for NRG-1β addition. The data in this study imply that NRG-1β promotes neurite outgrowth and neuronal migration from DRG explants in vitro.

[1]  T. Shea,et al.  Selective accumulation of the high molecular weight neurofilament subunit within the distal region of growing axonal neurites. , 2001, Cell motility and the cytoskeleton.

[2]  A. Theibert,et al.  Functions of PI 3-kinase in development of the nervous system , 2002, International Journal of Developmental Neuroscience.

[3]  R. Saunders,et al.  Widespread expression of ErbB2, ErbB3 and ErbB4 in non-human primate brain , 2007, Brain Research.

[4]  Hua-xiang Liu,et al.  Neuronal Phenotype and Tyrosine Kinase Receptor Expression in Cocultures of Dorsal Root Ganglion and Skeletal Muscle Cells , 2009, Anatomical record.

[5]  F. Huang,et al.  Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons , 2007, Cell Biology and Toxicology.

[6]  T. Mars,et al.  Apoptosis in co-cultures of human muscle and rat spinal cord during the formation of the neuromuscular junction , 2001, Pflügers Archiv.

[7]  J. Kapfhammer,et al.  Neuregulin Signaling Is Dispensable for NMDA- and GABAA-Receptor Expression in the Cerebellum In Vivo , 2009, The Journal of Neuroscience.

[8]  H. Moore,et al.  Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components , 2008, The Journal of Neuroscience.

[9]  S. Murphy,et al.  Neuregulin signaling in neurons depends on ErbB4 interaction with PSD-95 , 2008, Brain Research.

[10]  J. Wyss,et al.  Neuregulin-1β induces neurite extension and arborization in cultured hippocampal neurons , 2004, Molecular and Cellular Neuroscience.

[11]  J. Loeb,et al.  NT-3 and CNTF exert dose-dependent, pleiotropic effects on cells in the immature dorsal root ganglion: neuregulin-mediated proliferation of progenitor cells and neuronal differentiation. , 2006, Developmental biology.

[12]  J. Loeb,et al.  Differential distribution of neuregulin in human brain and spinal fluid , 2009, Brain Research.

[13]  B. Ford,et al.  Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia , 2008, Brain Research.

[14]  T. Gotow,et al.  Neurofilaments in health and disease , 2000, Medical Electron Microscopy.

[15]  H. Pant,et al.  Cyclin-Dependent Kinase 5 in Neurofilament Function and Regulation , 2003, Neurosignals.

[16]  B. Ford,et al.  Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression , 2005, Neurobiology of Disease.

[17]  Zhenzhong Li,et al.  Co-administration of Monosialoganglioside and Skeletal Muscle Cells on Dorsal Root Ganglion Neuronal Phenotypes In Vitro , 2009, Cellular and Molecular Neurobiology.

[18]  S. Carroll,et al.  ErbB Transmembrane Tyrosine Kinase Receptors Are Expressed by Sensory and Motor Neurons Projecting into Sciatic Nerve , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[19]  G. Devries,et al.  Developmental Regulation of Neuregulin1 Isoforms and erbB Receptor Expression in Intact Rat Dorsal Root Ganglia , 2008, Neurochemical Research.

[20]  Gerald Fischbach,et al.  Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Taehyeon M. Cho,et al.  Neurofilament 200 as an Indicator of Differences Between Mipafox and Paraoxon Sensitivity in SY5Y Neuroblastoma Cells , 2004, Journal of toxicology and environmental health. Part A.

[22]  I. Alexander,et al.  Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons. , 2001, Human gene therapy.

[23]  D. Talmage.  Mechanisms of neuregulin action. , 2008, Novartis Foundation symposium.

[24]  B. Ford,et al.  Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke. , 2004, Biochemical and biophysical research communications.

[25]  E. Lo,et al.  Neuregulin-1 Signaling in Brain Endothelial Cells , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  P. Wong,et al.  Pathogenesis of two axonopathies does not require axonal neurofilaments , 1998, Nature.

[27]  C. P. Robertson,et al.  The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion , 1997, The Journal of Neuroscience.

[28]  B. Ford,et al.  Extended Therapeutic Window and Functional Recovery after Intraarterial Administration of Neuregulin-1 after Focal Ischemic Stroke , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  E. Shohami,et al.  Closed Head Injury Induces Up-Regulation of ErbB-4 Receptor at the Site of Injury , 2000, Molecular and Cellular Neuroscience.

[30]  Fei Yang,et al.  The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant , 2008, Molecular pain.

[31]  S. Higashiyama,et al.  Regulation of Neuregulin Expression in the Injured Rat Brain and Cultured Astrocytes , 2001, The Journal of Neuroscience.