MECHANISMS OF TRANSPORT FROM OLFACTORY NEURONS TO CNS

现在有证据表明，一些无机分子、病毒、凝集素， 氨基酸和染料进入外鼻孔，由 嗅觉感受器神经元随后在中枢神经系统中被发现。 然而，这些现象的普遍性和背后的机制 没有得到系统的接洽。将物质输送到 支持内化的细胞表面蛋白或受体 外加分子。拟议中的实验将测试 假设两者的可识别的分子特征 应用物质和感受器神经元是运输所需的物质。 分子，特别是跨神经的，从鼻孔进入中枢神经系统。至 建议：1)检测凝集素的摄取和转运的特异性 嗅觉上皮细胞类型的分布。成虫 单侧鼻孔闭合也将被用来检查 气味对吸收和运输过程的刺激。2)确定 如果抗血清(neu-type)，识别表位在 嗅觉感受器神经元，优先内化和 被传输到大脑。转基因小鼠，表达独特的THY-1 他们受体细胞上的表位将被用来探索抗体特异性 摄取和运输。3)检查推定的多巴胺受体特异性 集中在嗅觉粘膜中。4)调查后果 关于外加分子的内化和运输 细胞存活和神经递质基因表达的关系。建议数 实验对神经元的机制有影响 将分子内化并将其运输到 神经元。认为嗅觉系统可以起到 与退行性综合征有关的物质的进入途径，如 阿尔茨海默氏症隐含在拟议的目标中。

Evidence now exists that some inorganic molecules, viruses, lectins, amino acids and dyes enter the external nares, are internalized by olfactory receptor neurons and subsequently are found in the CNS. However, the generality of and mechanisms underlying these phenomena have not been approached systematically. The transport of substances into the CNS may be quite specific and require the presence of oligosaccharides, cell surface proteins or receptors to support internalization of externally applied molecules. The proposed experiments will test the hypothesis that identifiable molecular characteristics of both the applied substances and receptor neurons are required for the transport of molecules, especially transneuronally, from the nares into the CNS. To more precisely define these properties, the following experiments are proposed: 1) to examine the uptake and transport specificity of lectins with identified oligosaccharide binding affinities and restricted cell-type distributions within the olfactory epithelium. Adult unilateral naris closure also will be utilized to examine the role of odorant stimulation on the uptake and transport process. 2) to determine if antisera (NEU-type), that recognize epitopes specifically expressed on olfactory receptor neurons, are preferentially internalized and transported to the brain. Transgenic mice, that express a unique thy-1 epitope on their receptor cells will be used to explore antibody-specific uptake and transport. 3) to examine presumed dopamine receptor-specific internalization and transport of cocaine, a drug of abuse, that is concentrated in the olfactory mucosa. 4) to investigate the consequences of internalization and transport of externally applied molecules in terms of cell survival and neurotransmitter gene expression. The proposed experiments have implications for the mechanisms by which neurons internalize molecules and transport them as well as the consequences to the neurons. The hypothesis that the olfactory system may serve as a route of entry of substances implicated in degenerative syndromes such as Alzheimer's disease is implicit in the proposed aims.