| Co-Investigator(Kenkyū-buntansha) |
MIYAJIMA Atsushi University of Tokyo, Institute of Molecular and Cellular Bioscience, Professor, 分子細胞生物学研究所, 教授 (50135232)
SENBA Emiko Wakayama Medical University, Department of Anatomy & Neurobiology, Professor, 医学部, 教授 (00135691)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Oncostatin M(OSM) is a member of the interleukin(IL)-6 cytokine family, which is involved in definitive hematopoiesis, the development of liver, and local inflammation. However, little is known about the role of OSM in the nervous system. In situ hybridization shows that OSM receptor β (OSMR) mRNA was found in astrocytes of olfactory bulb, epithelial cells of choroid plexus, and meningeal cells in pia mater. Its gene expression was first observed in large neurons of the hypoglossal nucleus at embryonic day (E) 14.5, which was sustained until neonatal mice. OSMR mRNA and protein were mainly localized in the ventral subnucleus of the developing hypoglossal nucleus.
In the adult dorsal root ganglia (DRGs), OSMR was exclusively expressed in small-sized neurons. Approximately 28% of OSMR-positive neurons contained TrkA-immunoreactivity (-ir), 63% expressed Ret-ir. No neuropeptides, including substance P and calcitonin gene-related peptide, were contained in the neurons. Furthermore, all OSMR-positive neurons expressed both vanilloid receptor 1(TRPV1) and P2X3 purinergic receptor.
In the DRGs of the OSM-deficient mice, TRPV1- and P2X3-positive small-sized neurons were significantly decreased. OSM-deficient mice displayed significantly reduced noxious responses in models of acute thermal, mechanical, chemical, and visceral pain. Thus, OSM plays an essential role in the development of a subtype of nociceptive neurons in the DRGs.
Little is known about the neurotrophin dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. TRPV2 was. first expressed in DRG neurons at E 11.5, when neither TRPV1 nor TRPM8 were detected yet. TrkC was expressed in most of TRPV2-positive DRG neurons at E11.5 and E13.5. In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively. These results suggest that TRPV2 is expressed predominantly in the NT-3-dependent subpopulation of DRG neurons throughout the development and in adult mice.
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