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

1. PAF受体在多发性硬化症中的作用建立了多发性硬化症小鼠实验性变应性脑脊髓炎动物模型。与野生型（WT）小鼠相比，PAF受体缺陷（PAFR-KO）小鼠的临床评分明显降低，尽管两组之间受影响小鼠的比例和发病天数没有差异。这些数据提示PAF在eae的发病机制中起重要作用。PAF受体在伤害感觉中的作用当小鼠后爪受到有害的热刺激和化学刺激时，pafr - ko小鼠的疼痛反应明显低于WT小鼠。采用RT-PCR检测PAF受体mRNA在背根神经节神经元中的表达，背根神经节是肢体伤害性信息传递的主要传入神经。此外，在离体培养的背根神经节神经元中观察到钙对PAF的反应。这些数据表明PAF至少是通过调节初级传入神经元来增强痛觉的。PAF受体在神经递质释放中的作用利用小鼠海马切片，通过配对脉冲促进和强直后增强两种电生理实验检测了Schaffer侧- ca1突触的神经递质释放。结果表明，这两种突触前现象在PAFR-KO小鼠中被抑制。在用PAF拮抗剂WEB2086预处理的WT小鼠中，破伤风后增强也被抑制。总之，这些数据表明PAF促进突触前神经递质释放。

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.