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.

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We fed immature 1+ arctic charr with a single dose of methyl[203Hg]mercury (MeHg) and quantified distribution kinetics with a new and simple three-compartment caternary model having well-perfused viscera and blood as the central compartment (VB), whereas gut (G) and the rest of body (R) constituted the peripheral compartments. The model accurately described distribution kinetics of MeHg in the fish, using either data of MeHg content in compartments or blood concentration data. Despite the known fast translocation of MeHg between binding sites at the molecular level, its translocation rate between compartments was surprisingly slow, 27 days being needed to complete 95% of the transfer from gut to blood and 48 days for the subsequent transfer to compartment R. This probably results from a limitation of the stepwise transfer rate of MeHg from red blood cells, which contain most of blood MeHg, to plasma and then to tissues due to low plasmatic concentration of small mobile sulfhydryl ligands. The model presented is a convenient tool that could be used to compare the fate of MeHg and other organometals, such as butyltins and alkylleads, in various aquatic and terrestrial animal species.

LARSSON, B. and H. TJALVE. Studies on the melanin-affinity of metal ions. Acta physiol. scand. 1978. 104. 479-484. Melanin has a capacity to accumulate metal ions in vivo and in r i m . In the present study, the relative melanin-affinity of various metal ions has been determined in v i m by use of the bisquaternary ammonium compound paraquat as a reference ion. Paraquat has previously been shown to bind to melanin with ionic binding as the dominant mechanism of interaction. The relative melanin-affinity of the metal ions was determined by studying the ability of the metal ions to compete with paraquat forcombiningwith the melanin. Pigment from beef eyes and synthetic melanin prepared from L-DOPA with tyrosinase were used. The affinity for melanin of the metal ions increased with increasing valencies. The order of affinity of the alkali metals was Cs+ : > Rb+ -> K+ > Na+ > Li+ and of the alkaline earth metals Ba'+ -' Sr2+ > CaZ+ :-Mg2+. T1+ had a slightly higher affinity than the alkali metals. Pb2+ had the strongest affinity of the divalent cations and Cu2+ was next i n order. Ni", Co2+ and Mn2+ showed affinities in the mentioned order. La3+ and Gd3+, which are chemically similar although the former is diamagnetic and the latter paramagnetic, showed a similar affinity for the melanin, suggesting that it is the chemical and not the magnetic properties which determine the affinity. The studied metal ions showed the same order of affinity for the synthetic melanin as for the eye-melanin, suggesting that the protein moiety of the pigment granules plays a minor role in the binding of the metal ions. Melanin has been shown to contain numerous free carboxyl groups. The results are consistent with the hypothesis that the metal-ion binding of the melanin can be ascribed to a cation-exchange activity with the free carboxyl groups in the melanin polymer as the main binding-sites.

gamma-spectrometry and autoradiography were used to examine the axoplasmic flow of manganese in the olfactory nerves and to study the uptake of the metal in the brain after application of 54Mn2+ in the olfactory chambers of pikes. The results show that the 54Mn2+ is taken up in the olfactory receptor cells and is transported at a constant rate along the primary olfactory neurones into the brain. The maximal velocity for the transported 54Mn2+ was 2.90 +/- 0.21 mm/hr (mean +/- S.E.) at 10 degrees, which was the temperature used in the experiments. The 54Mn2+ accumulated in the entire olfactory bulbs, although most marked in central and caudal parts. The metal was also seen to migrate into large areas of the telencephalon, apparently mainly via the secondary olfactory axons present in the medial olfactory tract. A transfer along fibres of the medial olfactory tract probably also explains the labelling which was seen in the diencephalon down to the hypothalamus. The results also showed that there is a pathway connecting the two olfactory bulbs of the pike and that this can carry the metal. Our data further showed a marked accumulation of 54Mn2+ in the meningeal epithelium and in the contents of the meningeal sacs surrounding the olfactory bulbs. It appears from our study that manganese has the ability to pass the synaptic junctions between the primary and the secondary olfactory neurones in the olfactory bulbs and to migrate along secondary olfactory pathways into the telencephalon and the diencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

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109Cd2+ was applied in the olfactory chambers of pikes (Esox lucius) and the dynamics of the axoplasmic flow of the metal was determined in the olfactory nerves by gamma spectrometry and autoradiography. The results showed that the 109Cd2+ is transported at a constant rate along the olfactory nerves. The profile of the 109Cd2+ in the nerves showed a wave front of transported metal followed by a saddle region. When the nasal chambers were washed 2 hr after application of the 109Cd2+ well-defined transport peaks for the metal were seen in the olfactory axons. The maximal velocity for the transport of 109Cd2+, which corresponds to the movement of the wave front, was 2.38 +/- 0.10 mm/hr (mean +/- S.E.) at the experimental temperature (10 degrees C). The average velocity for the transport of the 109Cd2+, which corresponds to the peak apex movement of the wave, was 2.18 +/- 0.05 mm/hr (mean +/- S.E.) at 10 degrees C. The transported 109Cd2+ was strongly accumulated in the anterior parts of the olfactory bulbs, whereas in other brain areas the levels of the metal remained low. Autoradiography of a pike exposed to 109Cd2+ via the water showed a strong labelling in the receptor-cell-containing olfactory rosettes, whereas other structures in the olfactory chambers were only weakly labelled. The accumulation and axonal transport in the olfactory neurons may be noxious and constitute an important component in the toxicology of cadmium in fish, and this may apply also to some other heavy metals.