Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized (1)H MRS.
Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized (1)H MRS.
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DOI：
10.1016/j.nmd.2015.07.003
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Lovering RM
中科院分区：
文献类型：
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作者：
Xu S;Shi D;Pratt SJP;Zhu W;Marshall A;Lovering RM
杜氏肌营养不良症 (DMD) 是一种由肌营养不良蛋白缺乏引起的 X 连锁疾病，其特征是骨骼肌进行性萎缩。迄今为止，对肌营养不良蛋白功能的了解来源于对肌营养不良蛋白缺陷动物的研究，最常见的模型是 mdx 小鼠。大多数针对 DMD 患者和 mdx 小鼠的研究都集中在骨骼肌和逆转或至少减缓严重肌肉萎缩和进行性退化的疗法的开发上。然而，肌营养不良蛋白也在中枢神经系统中表达。 mdx 小鼠和 DMD 患者都会出现认知和行为变化，但对营养不良性大脑的研究有限。我们使用磁共振成像和光谱学 (MRI/MRS) 检查了成熟野生型 (WT) 和 mdx 小鼠的大脑结构和代谢物。在 mdx 大脑中观察到结构和代谢的改变。与 WT 小鼠相比，mdx 小鼠侧脑室增大。弥散张量成像显示前额皮质弥散扩散率升高，海马部分各向异性减少。代谢变化包括海马中磷酸胆碱和谷胱甘肽的升高以及γ-氨基丁酸的减少。此外，在前额皮质中观察到牛磺酸含量升高。这些发现表明，缺乏抗肌营养不良蛋白的大脑中存在区域结构变化、细胞抗氧化防御能力改变、GABA能神经传递功能障碍以及渗透调节紊乱。
Duchenne muscular dystrophy (DMD), an X-linked disorder caused by the lack of dystrophin, is characterized by the progressive wasting of skeletal muscles. To date, what is known about dystrophin function is derived from studies of dystrophin-deficient animals, with the most common model being the mdx mouse. Most studies on patients with DMD and in mdx mice have focused on skeletal muscle and the development of therapies to reverse, or at least slow, the severe muscle wasting and progressive degeneration. However, dystrophin is also expressed in the CNS. Both mdx mice and patients with DMD can have cognitive and behavioral changes, but studies in the dystrophic brain are limited. We examined the brain structure and metabolites of mature wild type (WT) and mdx mice using magnetic resonance imaging and spectroscopy (MRI/MRS). Both structural and metabolic alterations were observed in the mdx brain. Enlarged lateral ventricles were detected in mdx mice when compared to WT. Diffusion tensor imaging revealed elevations in diffusion diffusivities in the prefrontal cortex and a reduction of fractional anisotropy in the hippocampus. Metabolic changes included elevations in phosphocholine and glutathione, and a reduction in γ-aminobutyric acid in the hippocampus. In addition, an elevation in taurine was observed in the prefrontal cortex. Such findings indicate a regional structural change, altered cellular antioxidant defenses, a dysfunction of GABAergic neurotransmission, and a perturbed osmoregulation in the brain lacking dystrophin.