In the olfactory epithelium the primary olfactory neurones are in contact with the environment and via the axonal projections they are also connected to the olfactory bulbs of the brain. Therefore, the primary olfactory neurones provide a pathway by which foreign materials may gain access to the brain. In the present study we used autoradiography and gamma spectrometry to show that intranasal instillation of manganese (54Mn2+) in rats results in initial uptake of the metal in the olfactory bulbs. The metal was then seen to migrate via secondary and tertiary olfactory pathways and via further connections into most parts of the brain and also to the spinal cord. Intranasal instillation of cadmium (109Cd2+) resulted in uptake of the metal in the anterior parts of the olfactory bulbs but not in other areas of the brain. This indicates that this metal is unable to pass the synapses between the primary and secondary olfactory neurones in the bulbs. Intraperitoneal administration of 54Mn2+ or 109Cd2+ showed low uptake of the metals in the olfactory bulbs, an uptake not different from the rest of the brain. Manganese is a neurotoxic metal which in man can induce an extrapyramidal motor system dysfunction associated with occupational inhalation of manganese-containing dusts or fumes. We propose that the neurotoxicity of inhaled manganese is related to an uptake of the metal into the brain via the olfactory pathways. In this way manganese can circumvent the blood-brain barrier and gain direct access to the central nervous system.

During early infancy, rat pups are unable to down-regulate intestinal iron transporters or iron absorption in response to iron supplementation, whereas down-regulation occurs during late infancy. The current findings provide evidence of the developmental regulation of iron absorption, which emphasizes the need for caution when giving iron supplements to infants at an early age.

.-Two iron transporters, divalent metal transporter1 (DMT1) and ferroportin1 (FPN1) have been identified; however, their role during infancy is unknown. We investigated DMT1, FPN1, ferritin, and transferrin receptor expression, iron absorption and tissue iron in iron-deficient rat pups, iron-deficient rat pups given iron supplements, and controls during early (day 10) and late infancy (day 20). With iron deficiency, DMT1 was unchanged and FPN1 was decreased (Ϫ80%) at day 10. Body iron uptake, mucosal iron retention, and total iron absorption were unchanged. At day 20, DMT1 increased fourfold and FPN1 increased eightfold in the low-Fe group compared with controls. Body iron uptake and total iron absorption were increased, and mucosal iron retention was decreased with iron deficiency. Iron supplementation normalized expression levels of the transporters, body iron uptake, mucosal iron retention, and total iron absorption of the low-Fe group to those of controls at day 20. In summary, the molecular mechanisms regulating iron absorption during early infancy differ from late infancy when they are similar to adult animals, indicating developmental regulation of iron absorption.

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