The effects of neuregulin-1β on neuronal phenotypes of primary cultured dorsal root ganglion neurons by activation of PI3K/Akt.
Neuregulin-1β (NRG-1β) signaling has multiple functions in neurons. NRG-1 signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The neuropeptide- and neurofilament (NF)-immunoreactive (IR) neurons are two major phenotypical classes in dorsal root ganglion (DRG). Whether NRG-1β influences DRG neuronal phenotypes remains unknown. To assess the effects of NRG-1β on DRG neuronal phenotypes, dissociated embryonic rat DRG neuronal culture model was established. Primary cultured DRG neurons were exposed to NRG-1β (5nmol/L), NRG-1β (10nmol/L), NRG-1β (20nmol/L), NRG-1β (20nmol/L) plus LY294002 (10μmol/L) for 3 days, respectively. The DRG neurons were continuously exposed to growth media as control. After that, all above cultured DRG neurons were processed for double fluorescent labeling of calcitonin gene-related peptide (CGRP) or neurofilament-200 (NF-200) and microtubule associated protein 2 (MAP2). The percentage of CGRP-IR neurons and NF-200-IR neurons was counted. The expression of CGRP mRNA and NF-200 mRNA was analyzed by real time-PCR analysis. The percentage of CGRP-IR neurons but not NF-200-IR neurons increased significantly in the presence of NRG-1β as compared with that in the absence of NRG-1β. The levels of CGRP mRNA but not NF-200 mRNA increased significantly in the presence of NRG-1β as compared with that in the absence of NRG-1β. PI3K inhibitor LY294002 blocked the effects of NRG-1β. These results support an important role for exogenous NRG-1β in induction of the distinct neuronal phenotype response by activation of PI3K/Akt in sensory neurons.
Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China.
Zhen
Z
Liu
Hao
H
Jiang
Hao
H
Li
Huaxiang
H
Liu
Xiaobo
X
Xu
Zhenzhong
Z
Li
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D020890:Neuregulin-1 / Q000494:pharmacology*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D002867:Chromones; D004791:Enzyme Inhibitors; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D020890:Neuregulin-1; D016900:Neurofilament Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C117467:neuregulin beta; C051774:neurofilament protein H; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D015740:Calcitonin Gene-Related Peptide