Analysis of functions of platelet-activating factor (PAF) in nervous system

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1. Role for PAF receptor in multiple sclerosisExperimental 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 nociceptionPAFR-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 releaseUsing 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.