Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy
Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy
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DOI：
10.1152/japplphysiol.01327.2006
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发表时间：
2007-06-01
影响因子：
3.3
通讯作者：
Heerschap, Arend
中科院分区：
文献类型：
--
作者：
Kan, Hermien E.;Meeuwissen, Esther;Heerschap, Arend
以2 g·kg体重（-1）的剂量补充Cr后，研究了由胍基乙酸甲基转移酶缺失（GAMT（-/-））引起的Cr缺乏小鼠模型骨骼肌和脑中的肌酸（Cr）水平。d（-1）Cr，持续35天。在补充Cr之前和之后的GAMT（-/-）小鼠和对照（Con）小鼠的脑（小脑和丘脑/海马）和后莱亚肌中进行局部H-1磁共振波谱（MRS）。正如预期的那样，在Cr补充之前，在GAMT（-/-）小鼠的MR谱中几乎检测不到Cr的信号。在这些小鼠的丘脑/海马区中，观察到N-乙酰丙酸（NAA）增加。在铬管理，铬水平增加更快的骨骼肌相比，大脑，但这只发生在第一天的补充。此后，铬水平增加了0.8毫米/天，在所有研究的位置。经过35天的铬补充，铬水平在所有位置均高于Con小鼠无铬饮食和NAA水平正常化。仅由于在GAMT（-/-）小鼠的纵向Cr补充研究中进行的重复MRS测量，我们才能够发现与脑相比，骨骼肌中Cr的初始摄取更快，这可能代表肌肉Cr摄取独立于Cr转运蛋白表达。我们的研究结果可以为其他实验提供基础，以优化GAMT缺乏症的Cr补充，因为Cr补充后患者的脑Cr增加缓慢。
Creatine (Cr) levels in skeletal muscle and brain of a mouse model of Cr deficiency caused by guanidinoacetate methyltransferase absence (GAMT(-/-)) were studied after Cr supplementation with 2 g-kg body wt(-1.)day(-1) Cr for 35 days. Localized H-1 magnetic resonance spectroscopy (MRS) was performed in brain (cerebellum and thalamus/ hippocampus) and in hind lea muscle of GAMT(-/-) mice before and after Cr supplementation and in control (Con) mice. As expected, a signal for Cr was hardly detectable in MR spectra of GAMT(-/-) mice before Cr supplementation. In the thalamus/hippocampus region of these mice, an increase in N-acetylasparate (NAA) was observed. During Cr administration, Cr levels increased faster in skeletal muscle compared with brain, but this occurred only during the first day of supplementation. Thereafter, Cr levels increased by 0.8 mM/day in all studied locations. After 35 days of Cr supplementation, Cr levels in all locations were higher compared with Con mice on a Cr-free diet and NAA levels nomialized. Only because of the repeated MRS measurements perforrited in this longitudinal Cr supplementation study on GAMT(-/-) mice were we able to discover the initial faster uptake of Cr in skeletal muscle compared with brain, which may represent muscular Cr uptake independent of Cr transporter expression. Our results can provide the basis for additional experiments to optimize Cr supplementation in GAMT deficiency, as increases in brain Cr are slow in patients after Cr supplementation.