FUNCTION OF TAURINE IN THE PRIMARY OLFACTORY PATHWAY

University Of Pennsylvania, Philadelphia PA

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Abstract

In the mammalian central nervous system (CNS), the amino acid taurine is involved in a number of fundamental processes, including neuronal maturation, cell protection, neuronal inhibition, and neurotransmitter release. The primary olfactory pathway contains some of the highest concentrations of taurine in the CNS, and taurine is the most abundant amino acid in the olfactory epithelium and olfactory bulb. However, the physiological role of taurine in the olfactory system is unknown. Only recently it was found that taurine has modulatory effects on synaptic transmission from olfactory sensory neurons to bulbar cells. Rat nasal mucosa shows high gene expression of the rate-limiting enzyme of taurine biosynthesis, cysteine sulfinic acid decarboxylase (CSD). To investigate further the function of taurine in the primary olfactory pathway, the cellular sites of taurine synthesis and/or accumulation in the olfactory epithelium will be localized with specific antibodies, and taurine deficiency will be produced in this tissue. Antisense technology will be employed in order to inhibit the translation of CSD protein from specific mRNA and to reduce taurine production in the olfactory epithelium. Rats will receive microinfusion of antisense and control oligonucleotides into the nasal cavity. Effective doses of antisense oligonucleotides as well as the optimal duration and the specificity of antisense treatment will be established by measuring levels of CSD protein (Western blot) and concentrations of taurine and other amino acids (HPLC technique) in the nasal epithelium. The cellular targets or antisense oligonucleotides will be determined with fluorescein-labeled compounds. Following antisense treatment, functional characteristics of the olfactory system will be evaluated using recordings of the electro-olfactogram and sensitive behavioral tests (odor mixture discrimination and absolute detection threshold tasks). The number of mature sensory neurons in the epithelium and the density of their axons in the bulb will be determined by immunostaining for olfactory marker protein. Our working hypothesis is that taurine is localized in sensory neurons and serves to ensure maturation of newly generated cells. Taurine deficiency will decrease the number of mature sensory cells and produce olfactory deficits. These studies will demonstrate the function of taurine in the olfactory epithelium and potential mechanisms of taurine action on primary olfactory neurons.