The olfactory system is known to manifest a progressive decline in both discrimination and sensitivity with aging. Some of the potential consequences of such alterations are impaired appetite with concomitant malnutrition, and inability to sense danger situations that have olfactory cues, e.g. fire. Odorant Binding Protein (OBP) has recently been purified from rat and cow. This protein is thought to concentrate odorants in the mucous blanket of the nose for delivery to the olfactory epithelium. Presumably, a decline in OBP could cause elevations in olfactory threshold and diminished olfactory discrimination. It is not known if OBP also declines with age. If so, then it could account for these observed changes in olfaction. Phase One of this study will histologically evaluate the rat's sole source of OBP, the lateral nasal gland, as a function of age. Other secretory glands will be similarly evaluated. Then, OBP from progressively aged rats will be purified according to an established protocol and have its equilibrium binding characteristics determined to see if an age-related change occurs. Finally, the amount and concentration of OBP in nasal secretions will be examined as function of age by a radioimmunoassay quantification method. The Second Phase of this project will apply the techniques developed in Phase One to the study of the role of OBP in human olfaction. This first goal of this phase is purification of OBP. The established purification scheme for rat will be used initially and modified if necessary. Once this protein is purified, then it can be biochemically characterized by equilibrium binding analysis. Its purification also allows the production of antibodies. These antibodies can be used then to localize the site of intranasal OBP production in humans immunohistochemically. These antibodies with purified, radiolabeled OBP can be used to develop a radioimmunoassay to quantify the amount and concentration of OBP in nasal secretions from patients. These levels, in conjunction with olfactory threshold and discrimination testing, will allow the determination of the role of OBP in human olfaction. Specifically, these parameters will be examined as a function of age to elucidate the role of OBP in the declining function of the aged olfactory system.
