Harmful Effects of Cadmium on Olfactory System in Mice

Abstract

The inhalation of certain metals can result in olfactory epithelial injury, an altered sense of smell, and direct delivery of the metal from the olfactory epithelium to the olfactory bulbs and other parts of the central nervous system. The purpose of this study was to examine whether mice given an intranasal instillation of cadmium would develop altered olfactory function and to assess whether cadmium may be transported directly from the olfactory epithelium to the central nervous system. To evaluate cadmium's ability to induce anosmia and on the basis of olfactory epithelium sensitivity to metals, the aim of this study was first to study cadmium effects on the olfactory function and secondly to check whether cadmium may be transported from the nasal area to the central nervous system. After an intranasal instillation of a solution containing CdCl 2 at 136 mM, we observed in treated mice: (1) a partial destruction of the olfactory epithelium, which is reduced to three or four basal cell layers followed by a progressive regeneration; (2) a loss of odor discrimination with a subsequent recovery; and (3) a cadmium uptake by olfactory bulbs demonstrated using atomic absorption spectrophotometry, but not by other parts of the central nervous system. Cadmium was delivered to the olfactory bulbs, most likely along the olfactory nerve, thereby bypassing the intact blood-brain barrier. We consider that cadmium can penetrate olfactory epithelium and hence be transported to olfactory bulbs. The olfactory route could therefore be a likely way to reach the brain and should be taken into account for occupational risk assessments for this metal.

Associations between Cadmium Exposure and Taste and Smell Dysfunction: Results from the National Health and Nutrition Examination Survey (NHANES), 2011–2014

“…Our findings were consistent with previous animal studies and population studies in occupational settings. In a mouse study, Bondier et al [35] found that the olfactory route was likely to be one way by which cadmium can reach the brain. Sulkowski et al [36] found significant associations between olfactory dysfunction and blood and urinary cadmium levels.…”

Intranasal exposure to uranium results in direct transfer to the brain along olfactory nerve bundles

“…Metals can also be mentioned. Olfactory uptake has been demonstrated for mercury , manganese , cobalt , zinc , thallium and cadmium in rats and mice.…”

Olfactory dysfunction revisited: a reappraisal of work-related olfactory dysfunction caused by chemicals

“…In another animal experiment, administration of 400 μg of CdCl 2 to mice by intranasal instillation resulted in partial damage to the olfactory epithelium, reversible loss of olfactory discrimination, and specific cadmium deposition in the olfactory bulb but not in other parts of the central nervous system [39]. Czarnecki et al [40] also observed anosmia in a behavioural test following intranasal instillation of a cadmium chloride solution in mice.…”

“…Over 1000 axons of olfactory receptor neurons with the same receptor type project onto the dendrites of a single mitral cell [138]. Cadmium and manganese can be detected in the bulbus olfactorius of animals (see above, [38, 39, 63, 68, 72]) and in humans: Baader (1952) was able to determine atrophy of the nasal mucous membrane and an intensive yellow colouring of the olfactory bulb following the autopsy of an affected worker exposed to cadmium, which led him to suspect that cadmium reached the brain via the olfactory pathway [146]. After MRT research on non-human primates exposed to aerosolised manganese sulfate (particle diameter: 1.04–2.12 μm) had already demonstrated transport of manganese via the olfactory pathway and accumulation of manganese in the olfactory bulb [147], increased deposition of manganese in the olfactory bulb was also detected on 7 welders by means of functional magnetic resonance tomography [63].…”