Transport of manganese via the olfactory pathway in rats:: Dosage dependency of the uptake and subcellular distribution of the metal in the olfactory epithelium and the brain

The dosage dependency of the uptake of Mn from the olfactory epithelium via olfactory neurons into the brain was studied after intranasal administration of the metal in rats. The results indicate that the Mn transport is saturable both regarding the uptake into the olfactory epithelium and the transfer to the olfactory bulb. Further, our data indicate that Mn moves relatively freely from the olfactory bulb to the olfactory cortex at an amount dependent on the level of influx into the bulb. The transport to the rest of the brain was related to the amounts in the olfactory bulb and the olfactory cortex, but the relative proportion reaching this area increased with increasing doses. Cell fractionations showed that the Mn was present both in the cytosol and in association with various cell constituents, Gel filtrations of the cytosol on a Superdex 30 column showed that about 20% of the Mn in the brain and about 3% in the olfactory epithelium was eluted together with high-molecular-weight materials (MW > 10,000), whereas the rest was eluted in the total volume and may represent unbound metal. It is likely that the metal has been loosely associated with protein(s) or other constituents at the application to the column, but that this association is too loose to be retained during the passage through the column, Our results show that the olfactory neurons provide a pathway with a considerable capacity to transport Mn into the brain. We propose that the neurotoxicity of inhaled Mn is related to an uptake via this route. (C) 1999 Academic Press.