Colchicine-Induced Disruption of Axonal Transport Affects Brain Uptakes of ²⁴Na, ²⁸Mg, ⁴³K, ⁴⁷Ca, ⁴⁸V, ⁶⁷Cu via Olfactory Pathway

Abstract

The olfactory system enables a direct transport of certain metal ions from the nasal cavity to the brain. There are two main pathways of the olfactory transport, which are axonal transport via the olfactory and trigeminal nerves and epithelial transport via extracellular fluid and the sustentacular cells. We previously demonstrated the direct brain uptakes of Mg²⁺ and K⁺ by the olfactory transport, however it was still unclear in which pathway these ions were transported. In the present study, to clarify the principal pathway of Mg²⁺ and K⁺ transport, we observed the interference in the olfactory transport of monovalent and divalent cations by colchicine, which cause destruction of microtubule and disrupt the axonal transport. A colchicine solution (0.38 mmol/ml) was instilled into the right nos- trils of mice (ICR) under ether anesthesia. After 1 and 3 h, a multitracer solution, which included ²⁴Na, ²⁸Mg, ⁴³K, ⁴⁷Ca, ⁴⁸V and ⁶⁷Cu, was administered to the mice in the same way. Six hour after multitracer administration, the mice were sacrificed, and then the blood, liver, ethmoturbinals, and brain were dissected. Subsequently, the brain was subdivided into three regions; the olfactory bulb, the forebrain region, the rest of brain region. As a result, ²⁸Mg and ⁶⁷Cu uptakes in the olfactory bulbs were reduced by colchicine pretreatment. On the other hand, as to ⁴³K and ⁴⁸V uptakes, no difference was observed between the control and colchicine pretreatment groups. Although the precise mechanisms of these two olfactory transports are still unclear, it was indicated that the ²⁸Mg²⁺ and ⁶⁷Cu²⁺ transports were mediated mainly by the axonal transport, and ⁴³K⁺ and ⁴⁸VO²⁺( ⁴⁸VO₂ ²⁺) transports were mediated mainly by the epithelial transport.