Sitter Beathe, Autti Taina, Tyynelä Jaana, Sonnewald Ursula, Bathen Tone F, Puranen Johanna, Santavuori Pirkko, Haltia Matti J, Paetau Anders, Polvikoski Tuomo, Gribbestad Ingrid S, Häkkinen Anna-Maija
SINTEF Unimed, Trondheim, Norway.
J Neurosci Res. 2004 Sep 1;77(5):762-9. doi: 10.1002/jnr.20123.
The neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.3-T high-resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS (1)H MRS technique in analysis of autopsy brain tissue. Ex vivo spectra from CLN1 autopsy brain tissue (n = 9) significantly differed from those of the control (n = 9) and CLN3 (n = 5) groups, although no differences were found between the CLN3 and the control groups. Principal component analysis of ex vivo data showed that decreased levels of N-acetylaspartate (NAA), gamma-aminobutyric acid (GABA), glutamine, and glutamate as well as increased levels of inositols characterized the CLN1 spectra. Also, the intensity ratio of lipid methylene/methyl protons was decreased in spectra of CLN1 brain tissue compared with CLN3 and control brain tissue. In concordance with the ex vivo data, the in vivo spectra of late-stage patients with CLN1 (n = 3) revealed a dramatic decrease of NAA and a proportional increase of myo-inositol and lipids compared with control subjects. Again, the spectra of patients with CLN3 (n = 13) did not differ from those of controls (n = 15). In conclusion, the ex vivo and in vivo spectroscopic findings were in good agreement within all analyzed groups and revealed significant alterations in metabolite profiles in CLN1 brain tissue but not in CLN3 compared with controls. Furthermore, HR MAS 1H MR spectra facilitated refined detection of neuronal metabolites, including GABA, and composition of lipids in the autopsy brain tissue of NCL patients.
神经元蜡样脂褐质沉积症（NCLs）是儿童中最严重的遗传性进行性神经退行性疾病之一。本研究的目的是比较婴儿型（CLN1）和青少年型（CLN3）NCL患者的体内1.5-T 1H磁共振（MR）和体外14.3-T高分辨率（HR）魔角旋转（MAS）1H MR脑谱，以获取有关这些疾病中神经元代谢物谱变化的详细信息，并测试体外HR MAS 1H MRS技术在尸检脑组织分析中的适用性。CLN1尸检脑组织（n = 9）的体外谱与对照组（n = 9）和CLN3组（n = 5）的谱有显著差异，尽管CLN3组与对照组之间未发现差异。体外数据的主成分分析表明，CLN1谱的特征是N-乙酰天门冬氨酸（NAA）、γ-氨基丁酸（GABA）、谷氨酰胺和谷氨酸水平降低以及肌醇水平升高。此外，与CLN3和对照脑组织相比，CLN1脑组织谱中脂质亚甲基/甲基质子的强度比降低。与体外数据一致，CLN1晚期患者（n = 3）的体内谱显示，与对照受试者相比，NAA显著降低，肌醇和脂质成比例增加。同样，CLN3患者（n = 13）的谱与对照组（n = 15）的谱没有差异。总之，体外和体内光谱学研究结果在所有分析组中都有很好的一致性，并且显示与对照组相比，CLN1脑组织中的代谢物谱有显著变化，而CLN3中没有。此外，HR MAS 1H MR谱有助于在NCL患者的尸检脑组织中精确检测包括GABA在内的神经元代谢物以及脂质成分。
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