In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7.
In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7.
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DOI：
10.1002/mds.26181
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发表时间：
2015-04-15
影响因子：
8.6
通讯作者：
Mochel, Fanny
中科院分区：
文献类型：
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作者：
Adanyeguh, Isaac M.;Henry, Pierre-Gilles;Nguyen, Tra M.;Rinaldi, Daisy;Jauffret, Celine;Valabregue, Romain;Emir, Uzay E.;Deelchand, Dinesh K.;Brice, Alexis;Eberly, Lynn E.;Oez, Guelin;Durr, Alexandra;Mochel, Fanny
脊髓小脑性共济失调(SCA)属于多谷氨酰胺重复障碍，以小脑和脑桥的萎缩为主要特征。用质子磁共振波谱(1HMRS)在3T条件下对SCA1(n=16)、SCA2(n=12)、SCA3(n=21)、SCA7(n=12)和健康对照组(n=33)进行了优化的半绝热定位，测定了SCA1(n=16)、SCA2(n=12)、SCA3(n=21)、SCA7(n=33)患者小脑疣和脑桥的代谢产物浓度。与对照组相比，患者的总N-乙酰天冬氨酸降低，谷氨酸降低，反映神经元丢失/功能障碍，而神经胶质标记物肌醇升高。另一种多谷氨酰胺重复疾病亨廷顿病的患者也表现出较高的总肌酸水平。共济失调评定量表与患者两个受累区域的神经代谢物之间有很强的相关性。主成分分析证实，蚯蚓和脑桥的神经元代谢物(总N-乙酰天冬氨酸和谷氨酸)与神经胶质代谢产物(肌醇)和能量代谢产物(总肌酸)以及疾病严重程度(运动评分)呈负相关。选择代谢物的神经化学图谱也允许从对照中分离SCA2和SCA3。在患者身上检测到的神经代谢谱是神经元和星形细胞隔室细胞特异性变化的基础，而这些变化是其他神经成像手段无法评估的。来自这两个隔室的代谢物之间的负相关性表明，代谢试图补偿SCA中的神经元损伤。由于这些生物标记物反映了细胞代谢的动态方面，它们是概念验证治疗试验的良好候选者。
Spinocerebellar Ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum and the pons. Proton magnetic resonance spectroscopy (1H MRS) using an optimised semiadiabatic localization by adiabatic selective refocusing (semi-LASER) protocol was performed at 3 T to determine metabolite concentrations in the cerebellar vermis and pons of a cohort of patients with SCA1 (n = 16), SCA2 (n = 12), SCA3 (n = 21), SCA7 (n = 12) and healthy controls (n = 33). Compared to controls, patients displayed lower total N-acetylaspartate and, to a lesser extent, lower glutamate, reflecting neuronal loss/dysfunction, while the glial marker, myo-inositol, was elevated. Patients also showed higher total creatine as reported in Huntington disease, another polyglutamine repeat disorder. There was a strong correlation between the Scale for the Assessment and Rating of Ataxia and the neurometabolites in both affected regions of patients. Principal component analyses confirmed that neuronal metabolites (total N-acetylaspartate and glutamate) were inversely correlated in the vermis and the pons to glial (myo-inositol) and energetic (total creatine) metabolites, as well as to disease severity (motor scales). Neurochemical plots with selected metabolites also allowed the separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected in patients underlie cell-specific changes in neuronal and astrocytic compartments that cannot be assessed by other neuroimaging modalities. The inverse correlation between metabolites from these two compartments suggests a metabolic attempt to compensate for neuronal damage in SCAs. Because these biomarkers reflect dynamic aspects of cellular metabolism, they are good candidates for proof-of-concept therapeutic trials.
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影响因子：
2.9
作者：
Boer, V. O.;van Lier, A. L. H. M. W.;Klomp, D. W. J.
通讯作者：
Klomp, D. W. J.
影响因子：
14.5
作者：
Guerrini, L;Lolli, F;Mascalchi, M
通讯作者：
Mascalchi, M
影响因子：
3.3
作者：
Deelchand, Dinesh K.;Adanyeguh, Isaac M.;Emir, Uzay E.;Nguyen, Tra-My;Valabregue, Romain;Henry, Pierre-Gilles;Mochel, Fanny;Oez, Guelin
通讯作者：
Oez, Guelin
影响因子：
3.5
作者：
Oez, Guelin;Iltis, Isabelle;Hutter, Diane;Thomas, William;Bushara, Khalaf O.;Gomez, Christopher M.
通讯作者：
Gomez, Christopher M.
影响因子：
3.3
作者：
Oez, Guelin;Tkac, Ivan
通讯作者：
Tkac, Ivan