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Mn2+ dynamics in manganese-enhanced MRI (MEMRI): Cav1.2 channel-mediated uptake and preferential accumulation in projection terminals

MPG-Autoren
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Bedenk,  Benedikt T.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Almeida-Correa,  Suellen
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Jurik,  Angela
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Dedic,  Nina
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Grünecker,  Barbara
Max Planck Institute of Psychiatry, Max Planck Society;

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Genewsky,  Andreas J.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Kaltwasser,  Sebastian F.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Riebe,  Caitlin J.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Deussing,  Jan Michael
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Czisch,  Michael
Max Planck Institute of Psychiatry, Max Planck Society;

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Wotjak,  Carsten T.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Zitation

Bedenk, B. T., Almeida-Correa, S., Jurik, A., Dedic, N., Grünecker, B., Genewsky, A. J., et al. (2018). Mn2+ dynamics in manganese-enhanced MRI (MEMRI): Cav1.2 channel-mediated uptake and preferential accumulation in projection terminals. NEUROIMAGE, 169, 374-382. doi:10.1016/j.neuroimage.2017.12.054.


Zitierlink: https://hdl.handle.net/21.11116/0000-0001-8BEE-7
Zusammenfassung
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca2+ and Mn2+ to map the brain's activity in vivo. However, to what extent different Ca2+ channels contribute to the enhanced signal that MEMRI provides and how Mn2+ dynamics influence Mn2+ brain accumulation after systemic administration of MnCl2 are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca2+ channel 1.2 (Ca(v)1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl2 injections, as compared to control mice. In contrast, genetic deletion of L-type Ca2+ channel 1.3 (Ca(v)1.3) did not reduce signal. Brain structure-or cell type-specific deletion of Ca(v)1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mn2+ in projection terminals, which was confirmed by local MnCl2 administration to defined brain areas. Taken together, we provide unequivocal evidence that Ca(v)1.2 represents an important channel for neuronal Mn2+ influx after systemic injections. We also show that after neuronal uptake, Mn2+ preferentially accumulates in projection terminals.