Olfactory system mucosa

In vertebrates the neurons for olfaction are located in the nose mucosa and consist of short neurons with a peripheral ending endowed with odorant receptors for a large number of molecules in the environment. Each receptor neuron only contains one odorant receptor and is connected directly with the olfactory lobe of the brain. The vertebrate olfactory system must cope with a staggering developmental problem how to connect millions of olfactory neurons expressing different odorant receptors to appropriate targets in the brain. 

Another hypothesis is that environmental chemicals gain access to the central nervous system via the olfactory and limbic pathways. The absence of a blood-brain barrier in the olfactory system could permit direct access of environmental chemicals through the nasal mucosa to the olfactory bulb. The olfactory and limbic systems are anatomically linked and participate directly and indirectly in the regulation of cognitive, endocrine, and immune functions. In this hypothesis, chemical exposure could induce lasting changes in limbic and neuronal activity and alter a broad spectrum of behavioral and physiological functions. 

By considering the role of timing of odorant delivery in biological olfaction (Rubin Cleland 2006), we have recently built a novel machine olfaction technology, termed an artificial olfactory mucosa , which demonstrates clearly a third principle of odour discrimination in artificial olfactory systems ... 

Biomarkers of nickel exposure and effects include nickel concentrations in feces and urine and changes in serum antibodies and serum proteins. Levels of camosine, a dipeptide, seem to reflect the extent of nickel-induced damage to olfactory mucosa of rats, although the rodent olfactory system is more resilient than is the human. Studies on the availability of trace levels of nickel in food and water and in air would be helpful to... 

Whole-body autoradiography of male Sprague-Dawley rats given intravenous injections (2.7 mg/kg bw) of 7V-nitroso[ C]diethanolamine showed an even distribution in most tissues except for tissue-bound radioactivity that was localized in the liver and the nasal olfactory mucosa. A lower level of labelling in the central nervous system probably indicated that 7V-nitrosodiethanolamine penetrated the blood-brain barrier poorly, while higher labelling in the kidney and urinary bladder may reflect elimination of 7V-nitroso[ C]diethanolamine in urine (Lofbeig Tjalve, 1985). 

No exposure-related clinical signs or lesions of systemic toxicity were observed in male and female Sprague-Dawley rats exposed by inhalation to w-butyl acrylate, at concentrations of 0, 15, 45 and 135 ppm [0, 86, 258 and 773 mg/m ] over 24 months (Reininghaus et al., 1991). Atrophy of the neurogenic epithelial cells and hyperplasia of reserve cells were observed in the nasal mucosa of all -butyl acrylate-treated animals. These changes were dose-related and mainly affected the anterior part of the olfactory epithelium. Opacity and neovascularization of the cornea were seen in the group exposed to 135 ppm /7-butyl acrylate. 

Nasal cavity —> olfactory mucosa also nasal cavity —> systemic circulation Direct from nose to brain Direct from nose to brain Direct from nose to brain Direct from nose to brain Nasal cavity —> CSF Nasal cavity —> CSF Direct from nose to brain via olfactory pathway... 

Rodriguez I, Feinstein P, Mombaerts P (1999) Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97 199-208 Rodriguez I, Greer CA, Mok MY, Mombaerts P (2000) A putative pheromone receptor gene expressed in human olfactory mucosa. Nat Genet 26 18-19 Rodriguez I, Del Punta K, Rothman A, Ishii T, Mombaerts P (2002) Multiple new and isolated families within the mouse superfamily of Vlr vomeronasal receptors. Nat Neurosci 5 134-140... 

Cajal RSy. 191 la. Olfactory apparatus Olfactory mucosa and olfactory bulb or first-order olfactory center. Histology of the nervous system, Vol. IL Translated by Swanson N, Swanson L (1995). New York Oxford Univ. Press pp. 532-554. 

Tjalve H, Henriksson J, Tallkvist J, et al. 1996. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol 79 347-356. 

Respiratory Effects. Respiratory tract irritation has been reported at concentrations as low as 216 ppm in volunteers exposed for 45 minutes to 2 hours (Rowe et al. 1952). At concentrations of >1,000 ppm, tetrachloroethylene is intensely irritating (Carpenter 1937 Rowe et al. 1952). Changes in pulmonary function tests were not observed in four male volunteers exposed to 0, 20, 100, or 150 ppm tetrachloroethylene for 7.5 hours/day, 5 days/week, for 1 week at each exposure concentration (Stewart et al. 1981). Exposure of mice to 300 ppm of tetrachloroethylene (300 ppm) for 6 hours/day for 5 days has resulted in degeneration of the olfactory and respiratory mucosa (Aoki et al. 1994). Respiratory effects were not reported in animals after oral exposure (NCI 1977). Environmental exposure to tetrachloroethylene in air or water is unlikely to pose a risk to the respiratory system. 

Adenyl cyclase systems isolated from mammals contain as a third component an additional guanosine triphosphate specific subunit and in all probability even more components whose function and structure are not known as yet. It is interesting to note that adenyl cyclases, Na-K-actlvated adenosine phosphatases (ATPases) have been located in the membrane of olfactory neurons and cAMP was found to have the highest concentration in man in the olfactory mucosa. 

The mode of stimulation of these two systems is different. It is well established that land dwelling vertebrates deliver gaseous odorants to the olfactory mucosa by inhaling or sniffing with the nose. The molecules that stimulate the main olfactory apparatus must... 

Furthermore, in this system it is also possible to follow the dynamic diffusion of airborne molecules through the sensing layer, giving rise to spatio-temporal response patterns resembling those observed in the olfaction of animal models. This feature can be adequately exploited to develop a sort of artificial olfactory mucosa [44]. 

The human oral cavity is potentially coimected to the nasal cavity by way of the buccopharynx (oropharynx), pharynx, and nasopharynx [1,2]. Under those circumstances in which this potential connection is open, the air movement of an exhalation that exits from the anterior nates (nostrils) can acquire odorants from the oral cavity and move them through the nasal cavity. If these odorants, while in the nasal cavity, reach the olfactory mucosa at a flow rate and concentration [3,4] that allow penetration to olfactory receptor neurons [5] and activation of these receptors such that sufficient central nervous system (CNS) responses develop, retronasal olfaction may occur. A limitation to the present understanding of retronasal olfaction is the absence of empirical or numerical models of retronasal odorant transport in adult humans. Such models have been published for orthonasal olfaction via the anterior nares [4,6] but are not presently available for retronasal olfaction (experimental airflow and odorant uptake analysis is in progress PW Scherer, personal communication, October 2002). 

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