The olfactory system is affected by steroid aerosol treatment in mice

Abstract

Asthma needs continuous treatment often for years. In humans, some drugs are administered via aerosol, therefore they come in contact with both respiratory and olfactory mucosa. We explored the possibility that antiasthma corticosteroid treatment could influence the olfactory function by passage through the nose. A group of mice was exposed twice daily for 42 days to fluticasone propionate aerosol and was compared with a control group. Olfactory behavior, respiratory mechanics, histology, and immunoreactivity in the olfactory system were assessed. Fluticasone-treated mice were slower in retrieving a piece of hidden food, but both groups were similarly fast when the food was visible. When a clearly detectable odor was present in the environment, all mice behaved in a similar way. Respiratory mechanics indices were similar in all mice except for the viscose resistance, which was reduced in fluticasone-treated mice. Olfactory mucosa of fluticasone-treated mice was thicker than that of controls. Slight but consistent differences in staining were present for Olfactory Marker Protein but not for other proteins. A mild impairment of olfactory function is present in mice chronically treated with fluticasone aerosol, apparently accompanied by slight modifications of the olfactory receptor cells, and suggests monitoring of olfactory function modifications in long-term steroid users.corticosteroid; behavior THE OLFACTORY SYSTEM IS CHARACTERIZED by a rapid turnover of receptor neurons, for which lifespan is ϳ1 mo, and a neuron turnover in the first relay station, the olfactory bulb (OB). The receptor axons make synapses with dendrites of mitral cells in the glomeruli (11). OB interneurons are continuously renewed by cells that differentiate from neural stem cells residing in the subventricular zone. They arrive into the OB via the rostral migratory stream and are subsequently integrated in OB circuits (25, 33). Other chemosensory organs are present in the nasal cavity, concurring to chemosensory perception (8,39). This dynamic network is sensitive to environmental challenges, which often result in mucosal damage that is subsequently reflected in OB, affecting olfactory sensitivity (9, 29).Pathological conditions of the airways may affect the olfactory performance. Both upper and lower airways diseases, for example allergic rhinitis and asthma, are treated with topical administration of corticosteroids. Fluticasone propionate (FP) is one of the most popular and safe treatments for both conditions (2) due to its hepatic metabolism that allows only a topic anti-inflammatory effect without adrenal suppression (31). Whereas the improvement in the pathological state is well-documented (in humans, see, for example, Refs. 13,24,30,34,37; in mice, Refs. 12,32), little is known about its possible effect on olfactory cells and in the subsequent olfactory performance.Corticosteroid inhalatory treatments are often long-lasting, therefore they may influence the quality of life of patients even if they induce only slight side effect. Inha...

Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

“…In both cases, the average latency to reach the hidden food was significantly longer than that of the same animals one week after Aβ application, and it was also longer than that of the control animals three and four weeks after vehicle injection (Figure 5). In another set of animals (n = 9 for each group), we performed control measurements to test whether or not the differences in the time to reach the hidden chocolate was due to changes in motivation to seek food [61-63]. First, we observed that the differences in the ability to find the hidden chocolate between control animals and those injected with Aβ was the same with or without a motivation imposed by hunger (Deprived for 24 h vs. normally fed; Figure 6A).…”

“…First, we observed that the differences in the ability to find the hidden chocolate between control animals and those injected with Aβ was the same with or without a motivation imposed by hunger (Deprived for 24 h vs. normally fed; Figure 6A). We also excluded the possibility that intrabulbar injection of Aβ induces motor deficits or motivational failure by finding no difference between control and experimental groups in the time required to reach a food pellet that was visible to the animals (Figure 6A [61]). Moreover, there was no difference between control animals injected with vehicle and animals with intrabulbar injection of Aβ when measuring parameters related to feeding, such as weight gain (Figure 6B) or food intake (Figure 6C [63]).…”

“…Seven days after surgery, animals were tested for olfactory function [20,59-61]. The fed rats were placed in a cage (24 × 20 × 45 cm) with clean sawdust covering the floor.…”

“…The maximum test time allowed was 600 s. For statistical analysis only the rats in which the perfusion injectors were located in the OB region were included. Based on previous reports, the test does not require food or water deprivation [59-62], although it can be performed after food-deprivation [20,61,62] with no evident differences between the two conditions [62]. In all cases, the inability to find (see pp 15-16 for explanation) the hidden food is interpreted as an alteration in the main olfactory bulb function [20,59-61].…”

“…Based on previous reports, the test does not require food or water deprivation [59-62], although it can be performed after food-deprivation [20,61,62] with no evident differences between the two conditions [62]. In all cases, the inability to find (see pp 15-16 for explanation) the hidden food is interpreted as an alteration in the main olfactory bulb function [20,59-61]. Alternatively, to exclude both motor deficits and motivational failure, we repeated the same “olfactory test” with a food pellet (normal chow) in a visible position in front of the rat [62].…”