| Project/Area Number |
13670134
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHII Satoshi The University of Tokyo, Graduate School of Medicine, Department of Biochemistry and Molecular Biology, Research Associate, 大学院・医学系研究科, 助手 (10300815)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | platelet-activating factor / PAF / Receptor / Multiple sclerosis / Nociception / Neurotransmitter release / Knock-out mouse / Experimental Allergic Encephalomyelitis / Paired-pulse facilitation / posttetanic potentiation / 海馬 / CA1 / spontaneous miniature post-synaptic potential |
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| Research Abstract |
1. Role for PAF receptor in multiple sclerosis
Experimental allergic encephalomyelitis, an animal model of multiple sclerosis, was evoked in mice. PAF receptor-deficient (PAFR-KO) mice exhibited significantly reduced clinical scores when compared with wild-type (WT) mice, although the ratio of affected mouse and day of onset were not different between two groups. These data suggest an important role of PAF in the pathogenesis of EAE.
2. Role for PAF receptor in nociception
PAFR-KO mice displayed significantly reduced pain responses than WT mice, when the mouse hind paws received noxious thermal and chemical stimuli. The expression of PAF receptor mRNA was detected by RT-PCR in dorsal root ganglion neurons, which are primary afferents for transmission of nociceptive information from limbs. In addition, the calcium response was observed in the in vitro culture of dorsal root ganglion neurons in response to PAF. These data suggest that PAF potentiates pain sensation, at least, by modulating primary afferent neurons.
3. Role for PAF receptor in neurotransmitter release
Using the mouse hippocampal slices, neurotransmitter release at Schaffer collateral-CA1 synapses was examined by two electrophysiological experiments : paired-pulse facilitation and posttetanic potentiation. The resulting data demonstrated that the two presynaptic phenomena were suppressed in PAFR-KO mice. Posttetanic potentiation was also suppressed in WT mice that were pretreated with WEB2086, a PAF antagonist. Together, these data suggest that PAF facilitates presynaptic neurotransmitter release.
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