| Project/Area Number |
18591263
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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 |
Dermatology
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| Research Institution | Meiji College of Oriental Medicine |
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Principal Investigator |
EBARA Satomi Meiji College of Oriental Medicine, Department of Anatomy, Lecturer (20203648)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAMOTO Kenzo Meiji University of Oriental Medicine, Department of Anatomy, Professor (20141509)
MATSUDA Junko Tokai University, Institute of Glycotechnology, Assistant Professor (60363149)
SUZUKI Kunihiko Tokai University, Institute of Glycotechnology, Professor (30384895)
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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 |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | cutaneous recentors / myelinated nerve fibers / trigeminal nerve system / demyelination / confocal laser scannina microscopy / three-dimensional analysis / electron microscopy / Merkel cell nerve endings / PGP9.5 / 皮膚感覚神経 / 三叉神経系 / F4 / 80 |
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| Research Abstract |
The motor end plates and all sensory nerve endings in the skin except those innervated by C-fibers are terminal tips of myelinated nerve fibers. We studied the morphological consequences of demyelination of the innervating nerves to those terminals. We used two mouse models of the classical human genetic myelin disorder Krabbe disease. Neither the twitcher mouse nor saposin A knockout mouse can degrade galactosylceramide, the most characteristic lipid of the myelin sheath, due to underlying genetic abnormalities. While both are excellent models of the human disease, the saposin A knockout mouse has a milder phenotype including a later onset, slower progression, and a longer life span. The pathology of these mice has been studied extensively but little is known about changes in nerve terminals.
We examined the trigeminal nerve system from the pons, through the trigeminal ganglion to the skin surrounding vibrissae taken at intervals during the entire life span of these mutants using the c
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onfocal and the transmission electron microscopy. Early pathological changes were first observed in the infraorbital nerve of twticher mice at one week after birth. Demyelination appeared generally more severe distally than proximally. However, the nerve terminals in the skin were generally well preserved even when the signs of myelin destruction such as thinning and bubbling of the myelin sheath, and infiltration of the globoid cells were present in the more proximal segments. Infiltration of swollen F4/80-positive dendritic cells was evident in more central regions but was relatively unremarkable in the skin until the end of the 3rd week. After the 4th week, swelling of the club-like endings and degeneration of the lanceolate or Merkel endings in some vibrissae were observed by light and electron microscopy. The motor endplate was relatively unaffected on the light microscopic level. The pathology of the nerve endings in the saposin A knockout mouse at the terminal stage was highly variable, ranging from near normal to severe degeneration. The findings suggested that demyelination and associated delayed nerve conduction velocity may have surprisingly little effect on the nerve terminals. Thus, our study sheds some light on the mechanism of nerve ending maintenance. Less
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