Impact of manganese on the hippocampus metabolism in the context of MEMRI: a proton HRMAS MRS study

作者:Daoust A*; Barbier E L; Bohic S; Stupar V; Maunoir Regimbal S; Fauvelle F
来源:Toxicology Research, 2015, 4(2): 376-384.
DOI:10.1039/c4tx00135d

摘要

Manganese enhanced MRI ( MEMRI) offers many possibilities such as tract tracing of neuronal pathways and functional imaging in vivo. This technique necessitates a direct or indirect acute injection of MnCl2 in the brain. Unfortunately, local concentrations of Mn2+ and its impact on metabolism after a single injection remain largely unknown. In this study, we combined in vivo MEMRI and ex vivo Proton High Resolution Magic Angle Spinning MRS ( H-1 HRMAS MRS) to investigate the delayed impact of Mn2+ on rat hippocampal metabolism. MEMRI images were acquired 24 h after MnCl2 injection in the dentate gyrus of the rat hippocampus at two different Mn2+ doses: low ( 8 nmol; n = 16) and high ( 500 nmol; n = 10). The low Mn2+ dose had almost no impact on hippocampal metabolism while the high dose altered the amplitude of several metabolites ( up to + 54% for Glu and - 71% for Asp). Moreover, at this high dose, the paramagnetic properties of Mn2+ led to a broadening of the resonances of several organic acids ( lactate, glutamate, N- acetyl aspartate etc.), suggesting a chelation of Mn2+ and an impact on Mn2+ relaxivity. Metabolite amplitudes were well correlated with the Mn2+ concentrations measured with an MRI T-1- map ( glutamate: R-2 = 0.8, p = 0.02; phosphoethanolamine: R2 = 0.9, p = 0.0004;.- aminobutyrate: R2 = 0.7, p = 0.005 and phosphocholine: R2 = 0.6, p = 0.04). To conclude, HRMAS is well suited to investigate Mn2+ impact on the metabolism. The low Mn2+ dose ( 8 nmol) usually used in the MEMRI experiment does not impact the hippocampal metabolism. The chelation of Mn2+ and its impact on relaxivity suggests an over- estimation of the Mn2+ concentration when measured through a T1 map.

  • 出版日期2015

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