In vivo evaluation of cellular activity in αCaMKII heterozygous knockout mice using manganese-enhanced magnetic resonance imaging (MEMRI).
In vivo evaluation of cellular activity in αCaMKII heterozygous knockout mice using manganese-enhanced magnetic resonance imaging (MEMRI).
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使用锰增强的磁共振成像（MEMRI）的αCAMKII杂合敲除小鼠中细胞活性的体内评估。
DOI：
10.3389/fnint.2013.00076
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发表时间：
2013
影响因子：
3.5
通讯作者：
Miyakawa T
中科院分区：
文献类型：
--
作者：
Hattori S;Hagihara H;Ohira K;Aoki I;Saga T;Suhara T;Higuchi M;Miyakawa T
α-钙/钙调蛋白依赖性蛋白激酶II(α-CaMKII)是一种主要在前脑，尤其是突触后密度表达的丝氨酸/苏氨酸蛋白激酶，在突触的可塑性和学习记忆中起着关键作用。αCaMKII杂合基因敲除小鼠表现出异常的情绪、攻击行为和认知障碍，被认为是精神疾病的动物模型。我们以前的研究表明，在突变小鼠的海马区、中央杏仁核和内侧前额叶皮质，暴露于电击或执行工作记忆任务后的即刻早期基因(IEGs)的表达减少。这些变化可能是由神经元信号转导障碍引起的；然而，目前仍不清楚这些区域的神经元活动是否减少。在这项研究中，我们进行了体内锰增强磁共振成像(MEMRI)，以评估αCaMKII HKO小鼠大脑中的局部细胞活动。全身应用MnCl2后24 h的MEMRI信号强度反映了Mn2+通过电压门控和/或配基门控钙通道等转运机制进入神经元和神经胶质细胞的功能增加。αCaMKII HKO小鼠在齿状回(DG)表现为MEMRI低信号，在分子、形态和电生理水平上几乎所有神经元都处于未成熟状态。相比之下，对这些突变小鼠的信号强度的分析显示，海马区CA1区的活动增加，这是一个对认知功能至关重要的区域。终纹床核(BNST)的信号强度也增加，这与焦虑有关。突变小鼠的这些变化可能是观察到的失调行为的原因，如认知缺陷和异常的焦虑样行为，这些症状类似于人类精神疾病中的症状。
The alpha-calcium/calmodulin-dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase predominantly expressed in the forebrain, especially in the postsynaptic density, and plays a key role in synaptic plasticity, learning and memory. αCaMKII heterozygous knockout (HKO) mice exhibit abnormal emotional and aggressive behaviors and cognitive impairments and have been proposed as an animal model of psychiatric illness. Our previous studies have shown that the expression of immediate early genes (IEGs) after exposure to electric foot shock or after performing a working memory task is decreased in the hippocampus, central amygdala, and medial prefrontal cortex of mutant mice. These changes could be caused by disturbances in neuronal signal transduction; however, it is still unclear whether neuronal activity is reduced in these regions. In this study, we performed in vivo manganese-enhanced magnetic resonance imaging (MEMRI) to assess the regional cellular activity in the brains of αCaMKII HKO mice. The signal intensity of MEMRI 24 h after systemic MnCl2 administration reflects functional increases of Mn2+ influx into neurons and glia via transport mechanisms, such as voltage-gated and/or ligand-gated Ca2+ channels. αCaMKII HKO mice demonstrated a low signal intensity of MEMRI in the dentate gyrus (DG), in which almost all neurons were at immature status at the molecular, morphological, and electrophysiological levels. In contrast, analysis of the signal intensity in these mutant mice revealed increased activity in the CA1 area of the hippocampus, a region crucial for cognitive function. The signal intensity was also increased in the bed nucleus of the stria terminalis (BNST), which is involved in anxiety. These changes in the mutant mice may be responsible for the observed dysregulated behaviors, such as cognitive deficit and abnormal anxiety-like behavior, which are similar to symptoms seen in human psychiatric disorders.