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Role of phosphorylation of ERK in induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal horn.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2006 Oct; Vol. 84 (5), pp. 934-43. - Publication Year :
- 2006
-
Abstract
- Previous works have shown that activation of extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential for long-term potentiation (LTP) in hippocampus. In the present study, the role of the ERK/CREB pathway in LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathologic pain, was investigated in adult rats. Western blotting analysis showed that the protein level of phosphorylated ERK (p-ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP induction, starting at 15 min and returning to control at 60 min after tetanic stimulation and that the protein level of p-CREB increased at 30 min, persisting for at least 3 hr after LTP induction. Double immunofluorescence staining showed that p-ERK and p-CREB were only located in neurons but not in glial cells in the spinal dorsal horn after LTP induction. More importantly, we found that spinal application of PD 98059 (100 microM), a selective MEK inhibitor, at 30 min before tetanic stimulation blocked LTP induction and prevented the increase in p-ERK and p-CREB in spinal dorsal horn. When applied 15 min after LTP induction, PD98059 reversed established LTP. The drug, however, did not affect the spinal LTP, when applied at 30 min after LTP. Our results suggested that activation of ERK/CREB pathway in spinal dorsal neurons is necessary for induction and maintenance of long-term potentiation of the C-fiber evoked field potentials.<br /> (Copyright 2006 Wiley-Liss, Inc.)
- Subjects :
- Animals
Blotting, Western methods
Cyclic AMP Response Element-Binding Protein metabolism
Dose-Response Relationship, Radiation
Electric Stimulation methods
Enzyme Inhibitors pharmacology
Flavonoids pharmacology
Functional Laterality
Gene Expression Regulation, Enzymologic drug effects
Gene Expression Regulation, Enzymologic physiology
Immunohistochemistry methods
Long-Term Potentiation drug effects
Long-Term Potentiation radiation effects
Male
Nerve Fibers, Unmyelinated drug effects
Nerve Fibers, Unmyelinated radiation effects
Phosphorylation
Posterior Horn Cells drug effects
Posterior Horn Cells radiation effects
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Signal Transduction physiology
Signal Transduction radiation effects
Spinal Cord physiology
Time Factors
Extracellular Signal-Regulated MAP Kinases physiology
Long-Term Potentiation physiology
Nerve Fibers, Unmyelinated physiology
Posterior Horn Cells enzymology
Spinal Cord cytology
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 84
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 16902997
- Full Text :
- https://doi.org/10.1002/jnr.21013