A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Eur J Neurosci. 2009 Dec;30(11):2143-50. doi: 10.1111/j.1460-9568.2009.07015.x. Epub 2009 Nov 20.
We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased N-acetyl aspartate and glutamate and increased glutamine, taurine and myo-inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild-type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%), reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on N-acetyl aspartate loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention, leading to a 13% increase in weight between 120 and 130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models.
我们使用体内和体外磁共振波谱（MRS）研究了家族性肌萎缩侧索硬化症（FALS；G93A 模型）突变小鼠模型中疾病进展对脑区神经化学的影响。脑谱有许多依赖于脑区的变化。在大约 80 天龄的早期时间点，脑内谷氨酸增加。在后期时间点，变化更为广泛，包括 N-乙酰天冬氨酸和谷氨酸减少，谷氨酰胺、牛磺酸和肌醇增加。疾病的影响在脊髓中最为严重，其次是延髓，然后是感觉运动皮层。作为对照区域的小脑没有变化。在延髓、小脑和皮质中测量了饮食中补充肌酸（2%）对野生型和 FALS 动物的影响。大脑肌酸的增加在小脑（25%）最大，其次是延髓（11%），然后是皮层（4%），反映了肌酸激酶活性的顺序。在晚期，肌酸对延髓中 N-乙酰天冬氨酸丢失有保护作用。肌酸补充对体重保留有积极影响，导致 120 至 130 天之间体重增加 13%。MRS 有望监测 ALS 和 ALS 模型中多种神经保护策略的多个方面。
