Lee Do-Wan, Kwon Jae-Im, Woo Chul-Woong, Heo Hwon, Kim Kyung Won, Woo Dong-Cheol, Kim Jeong Kon, Lee Dong-Hoon
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.
Diagnostics (Basel). 2020 Dec 30;11(1):45. doi: 10.3390/diagnostics11010045.
This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate ( = 0.001), gamma-aminobutyric acid ( = 0.019), and glutamate + glutamine ( = 0.001); however, creatine + phosphocreatine ( = 0.006) and myo-inositol ( = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine ( < 0.001), glutamate/total creatine ( < 0.001), and GABA/total creatine ( = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.
本研究使用体内7T质子磁共振波谱定量测量了用铜螯合剂诱导的脱髓鞘大鼠模型海马病变中代谢物的变化。将19只Sprague Dawley大鼠随机分为两组，分别给予正常饲料或铜螯合剂（0.2%，w/w），持续7周。使用7T磁共振成像扫描仪对脱髓鞘海马病变进行定量测量。对所有质子谱进行代谢物浓度和相对比率的定量分析。与对照组相比，铜螯合剂诱导组大鼠的谷氨酸（P = 0.001）、γ-氨基丁酸（P = 0.019）和谷氨酸+谷氨酰胺（P = 0.001）浓度显著更高；然而，肌酸+磷酸肌酸（P = 0.006）和肌醇（P = 0.001）浓度更低。此外，我们发现铜螯合剂处理组大鼠的谷氨酰胺和谷氨酸复合物/总肌酸（P < 0.001）、谷氨酸/总肌酸（P < 0.001）以及GABA/总肌酸（P = 0.002）比率显著高于对照组大鼠。我们的结果表明，铜螯合剂诱导的神经元脱髓鞘可能影响海马病变中的严重异常代谢，这些反应可能由小胶质细胞激活、线粒体功能障碍和星形胶质细胞坏死引起。
