Neuregulin-1β Regulates the migration of Different Neurochemical Phenotypic Neurons from Organotypically Cultured Dorsal Root Ganglion Explants

Neuregulin-1 beta (NRG-1 beta) has multiple roles in the development and function in the nervous system and exhibits potent neuroprotective properties. In the present study, organotypically cultured dorsal root ganglion (DRG) explants were used to evaluate the effects of NRG-1 beta on migration of two major phenotypic classes of DRG neurons. The signaling pathways involved in these effects were also determined. Organotypically cultured DRG explants were exposed to NRG-1 beta (20 nmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (10 mu mol/L) plus NRG-1 beta (20 nmol/L), the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 (10 mu mol/L) plus NRG-1 beta (20 nmol/L), and LY294002 (10 mu mol/L) plus PD98059 (10 mu mol/L) plus NRG-1 beta (20 nmol/L), respectively, for 3 days. The DRG explants were continuously exposed to culture media as a control. After that, all above cultures were processed for detecting the mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real-time PCR analysis. CGRP and NF-200 expression in situ was determined by fluorescent labeling technique. The results showed that NRG-1 beta elevated the mRNA and protein levels of CGRP and NF-200. NRG-1 beta also increased the number and the percentage of CGRP-immunoreactive (IR) migrating neurons and NF-200-IR migrating neurons. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1 beta. The contribution of NRG-1 beta on modulating distinct neurochemical phenotypic plasticity of DRG neurons suggested that NRG-1 beta signaling system might play an important role on the biological effects of primary sensory neurons.