Uptake of metals in the brain via olfactory pathways

In the olfactory epithelium the dendrites of the primary olfactory neurons are in contact with the nasal lumen, and via the axons these neurons are also connected to the olfactory bulbs of the brain. Materials which come into contact with the olfactory epithelium can be taken up in the primary olfactory neurons and be transported to the olfactory bulbs and even further into other areas of the brain. The present review deals with the mechanism of uptake and transport of metals in the olfactory system. Metals discussed are mainly manganese, cadmium, nickel and mercury. Among the metals so far examined, manganese has been found to have a unique capacity to be taken up via the olfactory pathways and pass transneuronally to other parts of the brain. It is considered that the occupational neurotoxicity of inhaled manganese may be related to an uptake of the metal into the brain via the olfactory pathways. Studies with nickel indicate that this metal, following a transport to the terminal parts of the primary olfactory neurons in the glomeruli of the bulbs, slowly passes to secondary and tertiary olfactory neurons. Cadmium and mercury are transported along the primary olfactory neurons to their terminations in the olfactory bulbs, but these metals appear unable to continue along secondary olfactory neurons. Occupational inhalation of nickel or cadmium can be toxic to the olfactory sense. It is not yet known whether mercury is toxic to the olfactory system in mammals, but this metal is known to alter olfaction and olfactory-related behaviour in fish. Data in the literature dealing with a potential olfactory-related neurotoxicity of aluminum are also discussed in the paper.