MECHANISMS OF TRANSPORT FROM OLFACTORY NEURONS TO CNS

从嗅觉神经元到中枢神经系统的运输机制

• 批准号: 3218317
• 负责人: Harriet D. Baker
• 金额: $ 11.99万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3218317
• 关键词: antiserum; central nervous system; cocaine; dopamine; dopamine receptor; epithelium; epitope mapping; gene expression; genetically modified animals; immunocytochemistry; laboratory mouse; laboratory rat; lectin; neurons; neurotransmitters; olfactory lobe; olfactory nerve; olfactory stimulus

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.

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已经 没有被系统地接触过。 将物质输送到 中枢神经系统可能非常特殊，需要寡糖的存在， 细胞表面蛋白或受体支持内化 外部应用的分子。 拟议的实验将测试 假设可识别的分子特征 运输所需要的应用物质和受体神经元 分子，尤其是跨神经元，从鼻孔进入中枢神经系统。 到 更精确地定义这些属性，以下实验是 建议：1）检查凝集素的摄取和运输特异性 具有确定的寡糖结合亲和力和限制性 嗅觉上皮内的细胞类型分布。 成人 单侧鼻孔闭合也将用于检查 气味刺激吸收和运输过程。 2）确定 如果是抗血清（NEU型），则识别特异表达的表位 嗅觉受体神经元，优先内化并 输送到大脑。 表达独特 thy-1 的转基因小鼠 其受体细胞上的表位将用于探索抗体特异性 摄取和运输。 3) 检查假定的多巴胺受体特异性 可卡因（一种滥用药物）的内化和转运，即 集中于嗅粘膜。 4）调查后果 外部应用分子的内化和运输 细胞存活和神经递质基因表达。 拟议的 实验对神经元的机制有影响 内化分子并运输它们以及后果 神经元。 假设嗅觉系统可能充当 与退化综合征有关的物质的进入途径，例如 阿尔茨海默病隐含在拟议的目标中。