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Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury.
J Neurosci. 2003 May 15; 23(10):4117-26.JN

Abstract

To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons.

Authors+Show Affiliations

Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12764099

Citation

Obata, Koichi, et al. "Differential Activation of Extracellular Signal-regulated Protein Kinase in Primary Afferent Neurons Regulates Brain-derived Neurotrophic Factor Expression After Peripheral Inflammation and Nerve Injury." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 23, no. 10, 2003, pp. 4117-26.
Obata K, Yamanaka H, Dai Y, et al. Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. J Neurosci. 2003;23(10):4117-26.
Obata, K., Yamanaka, H., Dai, Y., Tachibana, T., Fukuoka, T., Tokunaga, A., Yoshikawa, H., & Noguchi, K. (2003). Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 23(10), 4117-26.
Obata K, et al. Differential Activation of Extracellular Signal-regulated Protein Kinase in Primary Afferent Neurons Regulates Brain-derived Neurotrophic Factor Expression After Peripheral Inflammation and Nerve Injury. J Neurosci. 2003 May 15;23(10):4117-26. PubMed PMID: 12764099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. AU - Obata,Koichi, AU - Yamanaka,Hiroki, AU - Dai,Yi, AU - Tachibana,Toshiya, AU - Fukuoka,Tetsuo, AU - Tokunaga,Atsushi, AU - Yoshikawa,Hideki, AU - Noguchi,Koichi, PY - 2003/5/24/pubmed PY - 2003/6/26/medline PY - 2003/5/24/entrez SP - 4117 EP - 26 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 23 IS - 10 N2 - To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/12764099/Differential_activation_of_extracellular_signal_regulated_protein_kinase_in_primary_afferent_neurons_regulates_brain_derived_neurotrophic_factor_expression_after_peripheral_inflammation_and_nerve_injury_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=12764099 DB - PRIME DP - Unbound Medicine ER -