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，被内化， 嗅觉受体神经元，随后在CNS中发现。 然而，这些现象的普遍性和机制， 没有被系统地对待。 将物质输送到 CNS可能是非常特异性的，需要寡糖的存在， 细胞表面蛋白或受体，以支持 外部应用分子。 拟议的实验将测试 这一假说认为， 应用的物质和受体神经元是运输所必需的。 分子，特别是经神经元，从鼻孔进入中枢神经系统。 到 为了更精确地定义这些性质，以下实验是 建议：1）检查凝集素的摄取和转运特异性 具有已鉴定的寡糖结合亲和力， 嗅上皮内的细胞类型分布。 成人 单侧鼻孔关闭也将用于检查 气味对吸收和运输过程的刺激。2)以确定 如果是抗血清（NEU-型），则识别表位特异性表达于 嗅觉受体神经元，优先内化， 传送到大脑。 转基因小鼠，表达独特的thy-1 其受体细胞上的表位将用于探索抗体特异性 吸收和运输。3)来检测多巴胺受体特异性 可卡因这种滥用药物的内在化和运输， 集中在嗅粘膜中。4)调查其后果 外部分子的内化和运输 细胞存活和神经递质基因表达。 拟议 实验对神经元 内化分子并运输它们， 神经元 嗅觉系统可能作为一种 参与退行性综合征的物质的进入途径， 阿尔茨海默氏病是隐含在拟议的目标。

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.