Manganese transport in the rat optic nerve evaluated with spatial‐ and time‐resolved magnetic resonance imaging

Abstract

Purpose: 1) To evaluate a novel theoretical model for in vivo axonal Mn 2þ transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data. Materials and Methods:Time-resolved in vivo T 1 -weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n ¼ 9) ON was obtained at different timepoints after intravitreal MnCl 2 injection. A concentration-dependent and a rate-dependent function for the Mn 2þ retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data.Results: The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn 2þ concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model. Conclusion:The results indicate that Mn 2þ input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn 2þ transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly.

Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese‐enhanced MRI (MEMRI)

“…contingent on a multitude of parameters, including rate of uptake of Mn 2þ at the injection site, density of axonal projections, and proximity to the cell body (17,21). In poikilothermic fish and frog species, this rate of uptake is significantly reduced to 1/4th-1/ 8th, depending on ambient temperature, and is estimated to be in the range of $0.25-0.50 mm/h.…”

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

“…Manganese-enhanced MRI (MEMRI) has been applied in the rodent CNS (Bearer et al, 2007; Chan et al, 2011; Olsen et al, 2010; Pautler et al, 1998; Thuen et al, 2008) to investigate ion homeostasis and axonal transport. Manganese ion (Mn 2+ ), as a calcium analogue, is taken up by neurons through voltage-gated Ca 2+ channels.…”

Olfactory Transport of Manganese: Implications for Neurotoxicity

“…25,26 Likewise, Lewis and coworkers 27 reported that the rat trigeminal nerve may also absorb and deliver manganese from the nasal cavity to the brain. The available data suggests that manganese ions that enter nerve cells are transported along the axons in an anterograde direction and also trans-synaptically, which allows for investigation of neural pathways and interneuronal connections in the olfactory system and elsewhere.…”