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

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Abstract

Neuregulin-1β (NRG-1β) 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-1β 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-1β (20 nmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (10 μmol/L) plus NRG-1β (20 nmol/L), the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 (10 μmol/L) plus NRG-1β (20 nmol/L), and LY294002 (10 μmol/L) plus PD98059 (10 μmol/L) plus NRG-1β (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-1β elevated the mRNA and protein levels of CGRP and NF-200. NRG-1β 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-1β. The contribution of NRG-1β on modulating distinct neurochemical phenotypic plasticity of DRG neurons suggested that NRG-1β signaling system might play an important role on the biological effects of primary sensory neurons.

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Abbreviations

CGRP:

Calcitonin gene-related peptide

CNS:

Central nervous system

CNTF:

Cholinergic neurotrophic factor

DMEM/F-12:

Dulbecco’s modified Eagle medium with F-12 supplement

DRG:

Dorsal root ganglion

DRGs:

Dorsal root ganglia

E:

Embryonic day

ERK1/2:

Extracellular signal-regulated protein kinase

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

IR:

Immunoreactive

MAP2:

Microtubule-associated protein 2

NC:

Nitrocellulose

NF:

Neurofilament

NF-200:

Neurofilament-200

NRG-1:

Neuregulin-1

NT-3:

Neurotrophin-3

pAkt:

Phosphorylated Akt

PBS:

Phosphate buffer saline

pERK1/2:

Phosphorylated ERK1/2

PI3K:

Phosphatidylinositol 3-kinase

PNS:

Peripheral nervous system

PSN:

Primary sensory neurons

SDH:

Spinal dorsal horn

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Acknowledgments

This work was supported by the Shandong Provincial Natural Science Foundation of China (No. ZR2013HM082).

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The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Cardiosurgery, Shandong University Qilu Hospital, 107 West Wenhua Xi Road, Jinan, 250012, Shandong Province, China

    Yunfeng Li & Yanwen Bi

  2. Department of Histology and Embryology, Binzhou Medical College, Binzhou, 256603, China

    Guixiang Liu

  3. Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, 250012, China

    Hao Li

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  1. Yunfeng Li
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Correspondence to Yanwen Bi.

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Li, Y., Liu, G., Li, H. et al. Neuregulin-1β Regulates the migration of Different Neurochemical Phenotypic Neurons from Organotypically Cultured Dorsal Root Ganglion Explants. Cell Mol Neurobiol 36, 69–81 (2016). https://doi.org/10.1007/s10571-015-0221-7

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