MECHANISMS OF TRANSPORT FROM OLFACTORY NEURONS TO CNS

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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.