Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome.
Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome.
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DOI：
10.1016/j.neuroscience.2010.07.038
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发表时间：
2010-10-27
期刊：
影响因子：
3.3
通讯作者：
Siuzdak, G.
中科院分区：
文献类型：
--
作者：
Patti, G. J.;Shriver, L. P.;Wassif, C. A.;Woo, H. K.;Uritboonthai, W.;Apon, J.;Manchester, M.;Porter, F. D.;Siuzdak, G.
关键词：
胆固醇是细胞膜的重要组成部分，是正常脂质组织和细胞信号传导所必需的。虽然与维持血浆和外周组织中胆固醇稳态相关的机制已得到充分研究，但胆固醇生物合成在正常脑功能和发育中的作用和调节已被证明更具挑战性。 Smith-Lemli-Opitz 综合征 (SLOS) 是一种胆固醇合成疾病，其特征是 DHCR7（7-脱氢胆固醇还原酶）突变，损害 7-脱氢胆固醇 (7DHC) 还原为胆固醇，并导致神经认知缺陷，包括小脑发育不全和自闭行为。在这里，我们使用了一种新型的基于质谱的成像技术，称为阳离子增强纳米结构引发剂质谱（NIMS），用于原位检测生物组织中完整的胆固醇分子。我们提供了 SLOS (Dhcr7−/−) 小鼠模型中大脑甾醇定位的第一张图像。在 SLOS 小鼠中，7DHC 和残留胆固醇在异常发育的小脑和脑干中都有显着的定位。相比之下，1天大的健康幼鼠的胆固醇分布在整个大脑中，与成年小鼠相当。这项研究首次应用 NIMS 来定位病理组织内代谢的扰动，并证明异常的胆固醇生物合成可能对这些大脑区域的发育特别重要。
Cholesterol is an essential component of cellular membranes that is required for normal lipid organization and cell signaling. While the mechanisms associated with maintaining cholesterol homeostasis in the plasma and peripheral tissues have been well studied, the role and regulation of cholesterol biosynthesis in normal brain function and development have proven much more challenging to investigate. Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol synthesis characterized by mutations of DHCR7 (7-dehydrocholesterol reductase) that impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol and lead to neurocognitive deficits, including cerebellar hypoplasia and austism behaviors. Here we have used a novel mass spectrometry-based imaging technique called cation-enhanced nanostructure-initiator mass spectrometry (NIMS) for the in situ detection of intact cholesterol molecules from biological tissues. We provide the first images of brain sterol localization in a mouse model for SLOS (Dhcr7−/−). In SLOS mice, there is a striking localization of both 7DHC and residual cholesterol in the abnormally developing cerebellum and brainstem. In contrast, the distribution of cholesterol in 1-day old healthy pups was diffuse throughout the cerebrum and comparable to that of adult mice. This study represents the first application of NIMS to localize perturbations in metabolism within pathological tissues and demonstrates that abnormal cholesterol biosynthesis may be particularly important for the development of these brain regions.
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影响因子：
4.2
作者：
Korade, Zeljka;Kenworthy, Anne K.;Mirnics, Karoly
通讯作者：
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.95.14.8181
发表时间：
1998-07-07
影响因子：
11.1
作者：
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通讯作者：
Moebius, FF
影响因子：
56.9
作者：
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通讯作者：
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