OLFACTORY TRANSPORT: A DIRECT ROUTE OF DELIVERY OF INHALED MANGANESE PHOSPHATE TO THE RAT BRAIN

Abstract

Experiments examining the dosimetry of inhaled manganese generally focus on pulmonary deposition and subsequent delivery of manganese in arterial blood to the brain. Growing evidence suggests that nasal deposition and transport along olfactory neurons represents another route by which inhaled manganese is delivered to certain regions of the rat brain. The purpose of this study was to evaluate the olfactory uptake and direct brain delivery of inhaled manganese phosphate ( 54 MnHPO 4 ). Male, 8-wk-old, CD rats with either both nostrils patent or the right nostril occluded underwent a single, 90-min, nose-only exposure to a 54 MnHPO 4 aerosol (0.39 mg 54 Mn/m 3 ; MMAD 1.68 w m, σ g 1.42). The left and right sides of the nose, olfactory pathway, striatum, cerebellum, and rest of the brain were evaluated immediately after the end of the 54 MnHPO 4 exposure and at 1, 2, 4, 8, and 21 d postexposure with gamma spectrometry and autoradiography. Rats with two patent nostrils had equivalent 54 Mn concentrations on both sides of the nose, olfactory bulb, and striatum, while asymmetrical 54 Mn delivery occurred in rats with one occluded nostril. High levels of 54 Mn activity were observed in the olfactory bulb and tubercle on the same side (i.e., ipsilateral) to the open nostril within 1-2 d following 54 MnHPO 4 exposure, while brain and nose samples on the side ipsilateral to the nostril occlusion had negligible levels of 54 Mn activity. Our results demonstrate that the olfactory route contributes to 54 Mn delivery to the rat olfactory bulb and tubercle. However, this pathway does not significantly contribute to striatal 54 Mn concentrations following a single, short-term inhalation exposure to 54 MnHPO 4 .