| Project/Area Number |
18500269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
YAMANAKA Hiroki Hyogo College of Medicine, Faculty of Medicine, Instructor (20340995)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Koichi Hyogo College of Medicine, Faculty of Medicine, Professor (10212127)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | neurpnathic pain / cell adhesion molecules / L1-CAM / dorsal root gangliae / dorsal horn / synapse / plasticuty / post transcriptional regulation / シナプス可塑性 / MAP kinase / 翻訳後修飾 / cell adhesion / proteolysis / Dorsal root gamglia / dorsal horn synapse / synaptic reorganization / p38 MAPK / neuropathic pain |
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| Research Abstract |
The cell adhesion molecule L1 (L1-CAM) plays important functional roles in the developing and adult nervous system. Here we show that peripheral nerve injury induced dynamic post-transcriptional alteration of L1-CAM in the rat dorsal root ganglia (DRG) and spinal cord. Sciatic nerve transection (SCNT) changed the expression of L1-CAM protein but not L1-CAM mRNA. In DRG, SCNT induced accumulation of the L1-CAM into surface of somata, which resulted in the formation of immunoreactive (ir) ring structures in a number of unmyelinated C-fiber neurons. These neurons with L1-CAM ir ring structures were heavily co-localized with phosphorylated p38 MAPK. Western blot analysis revealed the increase of full-length L1-CAM and decrease of fragments of L1-CAM after SCNT in DRG. Following SCNT, L1-CAM ir profiles in the dorsal horn showed an increase mainly in pre-synaptic areas of laminae I-II with a delayed onset and co-localized with growth-associated protein 43. In contrast to DRG, SCNT increased the proteolytic 80 kDa fragment of L1-CAM and decrease of full-length of L1-CAM in the spinal cord. The intrathecal injection of L1-CAM antibody for the extracellular domain of L1-CAM inhibited activation of p38 MAPK and emergence of ring structures of L1-CAM ir in injured DRG neurons. Moreover, inhibition of extracellular L1-CAM binding by intrathecal administration of antibody suppressed the mechanical allodynia and thermal hyperalgesia induced by partial sciatic nerve transection. Collectively, these data suggest that the modification of L1-CAM in nociceptive pathways might be an important pathomechanism of neuropathic pain.
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