Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain:: a quantitative in vivo 1H and 31P magnetic resonance study
Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain:: a quantitative in vivo 1H and 31P magnetic resonance study
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DOI：
10.1111/j.1471-4159.2004.02599.x
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发表时间：
2004-09-01
影响因子：
4.7
通讯作者：
Heerschap, A
中科院分区：
文献类型：
--
作者：
in 't Zandt, HJA;Renema, WKJ;Heerschap, A
肌酸激酶（CK）催化atp -磷酸肌酸（PCr）交换被认为在大脑能量稳态中起关键作用。本研究利用非侵入性定量磁共振成像和光谱学技术，评估了该系统在没有细胞质B-CK （B-CK-/-）、线粒体普遍存在的CK （UbCKmit-/-）或两种同工酶（CK -/-）的转基因小鼠中部分或完全耗损的代谢和解剖学后果。磁共振成像显示，B-CK-/-小鼠的心室大小增加，但在UbCKmit或复合CK突变的动物中没有。缺乏单个CK同工酶的小鼠具有正常的高能代谢物和组织pH水平。在CK双敲除的大脑中，pH、ATP和Pi水平也正常，即使PCr已完全无法检测到。此外，总肌酸水平下降了20-30%，神经元n -乙酰-天冬氨酸化合物水平也有类似的增加。虽然ck本身并不均匀地分布在整个中枢神经系统中，但这些改变在不同的大脑区域是均匀和一致的。肌醇和谷氨酸峰值的变化似乎是突变类型和脑区域特异性的。我们的研究结果挑战了目前关于PCr-CK能量系统生物学意义的模型，并表明肌酸在大脑中具有多方面的作用。
Creatine kinase (CK)-catalysed ATP-phosphocreatine (PCr) exchange is considered to play a key role in energy homeostasis of the brain. This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy. MR imaging revealed an increase in ventricle size in a subset of B-CK-/- mice, but not in animals with UbCKmit or compound CK mutations. Mice lacking single CK isoenzymes had normal levels of high-energy metabolites and tissue pH. In the brains of CK double knockouts pH and ATP and Pi levels were also normal, even though PCr had become completely undetectable. Moreover, a 20-30% decrease was observed in the level of total creatine and a similar increase in the level of neuronal N-acetyl-aspartate compounds. Although CKs themselves are not evenly distributed throughout the CNS, these alterations were uniform and concordant across different brain regions. Changes in myo-inositol and glutamate peaks did appear to be mutation type and brain area specific. Our results challenge current models for the biological significance of the PCr-CK energy system and suggest a multifaceted role for creatine in the brain.