Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry.
Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry.
复制标题
通过串联成像质谱法可视化中枢神经系统组织切片中乙酰胆碱分布。
DOI：
10.1007/s00216-012-5988-5
复制
发表时间：
2012-06
影响因子：
4.3
通讯作者：
Yao, Ikuko
中科院分区：
文献类型：
--
作者：
Sugiura, Yuki;Zaima, Nobuhiro;Setou, Mitsutoshi;Ito, Seiji;Yao, Ikuko
通过成像质谱（IMS）的代谢物分布成像是神经化学领域中越来越多地使用的工具。由于大多数以前的IMS研究分析了较大代谢物种类的相对丰度，因此将其应用扩展到较小分子（如神经递质）非常重要。本研究旨在开发IMS应用程序，以可视化中枢神经系统组织切片中的神经递质分布。在这里，我们提出了两个必须解决的技术问题，以实现神经递质成像：（1）较低浓度的生物活性分子，与膜脂相比，需要更高的灵敏度和/或信号噪声（S/N）比信号检测，（2）神经递质的分子周转是迅速的，因此，组织制备程序应仔细进行，以尽量减少死后的变化。我们首先使用基质辅助激光解吸/电离（MALDI）质谱（MS）检测六种神经递质，并选择乙酰胆碱（ACh）作为研究模型，评估了固有的灵敏度和基质干扰。接下来，我们检查了ACh的单MS成像和MS/MS成像，发现通过MS/MS成像中从m/z 146到m/z 87的离子跃迁，ACh可以以高S/N比可视化。此外，我们发现脑样本的原位冷冻方法在有效像素的数量和图像对比度方面改善了IMS数据质量（即，灵敏度和动态范围）。因此，通过解决上述问题，我们证明了ACh的组织分布，最适合的正离子检测的IMS分子标本，以揭示其在中枢神经系统组织中的定位。
Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues.
登录
查看更多内容
影响因子：
4.1
作者：
Liu, HJ;Sañuda-Peña, MC;Cohen, SA
通讯作者：
Cohen, SA
影响因子：
4.8
作者：
Hirao, K;Hata, Y;Takai, Y
通讯作者：
Takai, Y
影响因子：
2.5
作者：
Ishii, K;Wong, JK;Sumikawa, K
通讯作者：
Sumikawa, K
影响因子：
7.4
作者：
Chaurand, P;Stoeckli, M;Caprioli, RM
通讯作者：
Caprioli, RM
影响因子：
3.3
作者：
Koizumi, S.;Yamamoto, S.;Namba, H.
通讯作者：
Namba, H.