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At concentrations sufficient for visualisation using MRI, manganese (Mn) is believed to behave as a calcium analogue. This study examines different concentrations of Mn for enhanced MR tract tracing. The premise of activity-dependent axonal transport was also examined by partial or complete blockade of retinal ganglion cell activity. Quantitative T(1) maps and semi-quantitative normalised signal intensities in the superior colliculi facilitated assessment of applied intraocular concentrations and activity dependence, respectively. Varying the concentration of applied Mn revealed a non-monotonic profile, with optimal, unfavourable and undesirable effects noted: 25 mM proved optimal, showing a maximal decrease in T(1), whereas 400 mM was associated with no terminal-field enhancement. The estimated vitreal concentration for optimal transport of Mn (2 mM) is substantially lower than that used in previous studies of the mouse. Both the partial blockade of inputs to 50% of retinal ganglion cells by a mGluR6 glutamate agonist and the complete blockade of all retinal ganglion cell activity with tetrodotoxin failed to decrease the relative enhancement in the superior colliculus. The failure to prevent axonal transport of Mn by blocking activity (and therefore theoretically the intracellular influx) appeared to be paradoxical. The optimal vitreal concentration of Mn has previously been shown to facilitate massive intracellular uptake of Mn, competitively blocking calcium, and 1 mM Mn blocks neurotransmission pre-synaptically. These results suggest that, at concentrations required for optimal Mn-enhanced MRI tract tracing in the visual system of the mouse, the uptake and transport of Mn may be dominated by passive mechanisms, which may also block neurotransmission.

Original publication

DOI

10.1002/nbm.1272

Type

Journal article

Journal

NMR Biomed

Publication Date

10/2008

Volume

21

Pages

859 - 867

Keywords

Animals, Contrast Media, Dose-Response Relationship, Drug, Female, Magnetic Resonance Imaging, Manganese, Mice, Mice, Inbred C57BL, Presynaptic Terminals, Visual Pathways