Max Planck Institute of Psychiatry, Dept. Stress Neurobiology & Neurogenetics, Kraepelinstr. 2-10, 80804 Munich, Germany; Max Planck Institute of Psychiatry, Core Unit Neuroimaging, Kraepelinstr. 2-10, 80804 Munich, Germany.
Max Planck Institute of Psychiatry, Dept. Stress Neurobiology & Neurogenetics, Kraepelinstr. 2-10, 80804 Munich, Germany.
Neuroimage. 2018 Apr 1;169:374-382. doi: 10.1016/j.neuroimage.2017.12.054. Epub 2017 Dec 19.
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca and Mn to map the brain's activity in vivo. However, to what extent different Ca channels contribute to the enhanced signal that MEMRI provides and how Mn dynamics influence Mn brain accumulation after systemic administration of MnCl are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca channel 1.2 (Ca1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl injections, as compared to control mice. In contrast, genetic deletion of L-type Ca channel 1.3 (Ca1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Ca1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mn in projection terminals, which was confirmed by local MnCl administration to defined brain areas. Taken together, we provide unequivocal evidence that Ca1.2 represents an important channel for neuronal Mn influx after systemic injections. We also show that after neuronal uptake, Mn preferentially accumulates in projection terminals.
锰增强磁共振成像（MEMRI）利用 Ca 和 Mn 的生物物理相似性来绘制大脑在体内的活动。然而，不同的 Ca 通道在多大程度上有助于 MEMRI 提供的增强信号，以及 Mn 动力学如何影响全身给予 MnCl 后 Mn 在大脑中的积累，目前还不完全清楚。在这里，我们证明中枢神经系统中缺乏 L 型 Ca 通道 1.2（Ca1.2）的小鼠在重复全身给予 MnCl 后，MEMRI 对比的增加幅度约为对照组的 50%。相比之下，L 型 Ca 通道 1.3（Ca1.3）的基因缺失并没有减少信号。Ca1.2 的脑结构或细胞类型特异性缺失与体素水平 MEMRI 分析相结合，揭示了 Mn 在投射末端的优先积累，这一点通过局部给予 MnCl 至特定脑区得到了证实。总之，我们提供了确凿的证据表明，Ca1.2 是全身注射后神经元 Mn 内流的重要通道。我们还表明，在神经元摄取后，Mn 优先在投射末端积累。
