Neurochemical profile of the developing mouse cortex determined by in vivo1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia

Neurochemical profile of the developing mouse cortex determined by in vivo1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia
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DOI:
10.1111/j.1471-4159.2010.07051.x
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发表时间:
2010-12-01
影响因子:
4.7
通讯作者:
Gruetter, Rolf
Gruetter, Rolf
中科院分区:
医学2区
文献类型:
--
作者:
Kulak, Anita;Duarte, Joao M. N.;Gruetter, Rolf

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大脑皮质的神经化学特征以特定的区域和时间发展,这可能会被精神病学和其他神经病理学所扭曲。临床前研究通常涉及实验性的小鼠模型。在本研究中,我们采用纵向研究设计,测定了C57BL/6小鼠的神经化学图谱,为正常发育的小鼠皮质提供一个参考框架。在出生后第10、20、30、60和90天,用14T活体质子核磁共振波谱测定了18种代谢物在前皮质和后皮质中的浓度。皮质发育的显著特征是高浓度代谢产物的改变,如N-乙酰天冬氨酸、谷氨酸、牛磺酸和肌酸。区域特异性表现为谷氨酰胺、天冬氨酸和胆碱浓度的早期变化。在成年动物中,N-乙酰天冬氨酸、肌酸和肌醇的浓度存在区域差异。在这项研究中,动物被暴露在反复的异氟醚麻醉中。其他实验表明,后者对行为或皮质神经化学特征没有重大影响。总而言之,在14T时实现的测量的高灵敏度和重复性使我们能够识别小鼠皮质内皮质区域的发育变化。
P>The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.