Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks.
Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks.
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DOI：
10.1002/nbm.3421
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发表时间：
2015-11
影响因子：
2.9
通讯作者：
Hyder F
中科院分区：
文献类型：
--
作者：
Kannurpatti SS;Sanganahalli BG;Herman P;Hyder F
线粒体Ca 2+摄取影响脑能量代谢和神经信号传导。鉴于脑线粒体细胞器的分布与血管密度有关，并且在脑区域之间差异很大，我们假设线粒体Ca 2+摄取在脑区域之间具有不同的生理影响。我们测试了这一假设，通过监测大脑的“内在活动”来自静息状态fMRI BOLD波动在不同的功能网络跨越体感皮层，尾壳核，海马，丘脑，在正常和扰动线粒体Ca 2+摄取状态。在11.7T下，Ru 360和山奈酚分别抑制或增强麻醉大鼠线粒体Ca ~（2+）摄取。令人惊讶的是，Ru 360对线粒体Ca 2+摄取的抑制和山奈酚的增强导致了频率域（频谱振幅）和时间域（静息状态功能连接; RSFC）中全脑内在活动的类似剂量依赖性降低。在线粒体Ca 2+摄取抑制或增强期间，静息状态fMRI-BOLD波动的频率和时间域类似的剂量依赖性降低的事实表明，线粒体Ca 2+摄取及其稳态可能强烈影响静息时脑的功能组织。有趣的是，静息状态下尾壳核和丘脑区域中的fMRI衍生的内在活性随着药物治疗剂量的增加而饱和得比在皮质和海马区域中观察到的药物诱导的趋势快得多。频谱振幅和RSFC如何随治疗而变化的区域差异表明，静息状态fMRI确定的各种RSFC网络内存在不同的神经元介导的自发神经元活动耦合。鉴于脑线粒体细胞器的分布与血管密度有关，我们测试了脑内不同线粒体功能影响的假设。在11.7T下监测特定静息态fMRI（R-fMRI）网络内跨越体感皮层、尾壳核、海马和丘脑的自发BOLD信号波动。线粒体功能状态在体内使用针对线粒体Ca 2+单向转运体的特定试剂进行扰动。我们观察到的区域差异R-fMRI活动表明不同的神经元活动耦合在不同的静息状态功能网络的不同介导的自发神经元活动。
Mitochondrial Ca2+ uptake influences both brain energy metabolism and neural signaling. Given that brain mitochondrial organelles are distributed in relation to vascular density and varies considerably across brain regions, we hypothesized different physiological impact of mitochondrial Ca2+ uptake across brain regions. We tested the hypothesis by monitoring brain ‘intrinsic activity’ derived from the resting state-fMRI BOLD fluctuations in different functional networks spanning the somatosensory cortex, caudate putamen, hippocampus, and thalamus, during normal and perturbed mitochondrial Ca2+ uptake states. In anesthetized rats at 11.7T, mitochondrial Ca2+ uptake was inhibited or enhanced respectively by treatments with Ru360 or kaempferol. Surprisingly, mitochondrial Ca2+ uptake inhibition by Ru360 and enhancement by kaempferol, led to similar dose-dependent decrease in brain-wide intrinsic activities in both the frequency domain (spectral amplitude) and temporal domain (resting state functional connectivity; RSFC). The fact that similar dose-dependent decreases in the frequency and temporal domains of the resting state fMRI-BOLD fluctuations during mitochondrial Ca2+ uptake inhibition or enhancement indicated that mitochondrial Ca2+ uptake and its homeostasis may strongly influence brain’s functional organization at rest. Interestingly the resting state fMRI-derived intrinsic activities in the caudate putamen and thalamic regions saturated much faster with increasing dosage by either drug treatments than the drug-induced trends observed in cortical and hippocampal regions. Regional differences in how the spectral amplitude and RSFC changed with treatment indicate distinct mitochondria-mediated spontaneous neuronal activity coupling within the various RSFC networks determined by resting state fMRI. Given that brain mitochondrial organelles are distributed in relation to vascular density, we tested the hypothesis of distinct mitochondrial functional impact within the brain. Spontaneous BOLD signal fluctuations within specific resting-state fMRI (R-fMRI) networks spanning the somatosensory cortex, caudate putamen, hippocampus, and thalamus was monitored at 11.7T. Mitochondrial functional state was perturbed in vivo using specific agents directed towards the mitochondrial Ca2+ uniporter. We observed regional differences in R-fMRI activity indicating distinct mitochondria-mediated spontaneous neuronal activity coupling in different resting state functional networks.