Probing the lipid chemistry of neurotoxin-induced hippocampal lesions using multimodal imaging mass spectrometry.
Probing the lipid chemistry of neurotoxin-induced hippocampal lesions using multimodal imaging mass spectrometry.
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DOI：
10.1002/sia.5418
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Ewing AG
中科院分区：
文献类型：
--
作者：
Hanrieder J;Karlsson O;Brittebo E;Malmberg P;Ewing AG
环境毒素β-N-甲氨基-L-丙氨酸（BMAA）与神经退行性疾病病理学有因果关系。在大鼠模型中，新生儿BMAA暴露导致海马结构的选择性摄取，并导致成年动物的学习和记忆障碍。此外，高剂量的新生儿BMAA暴露导致在成人海马CA 1区的蛋白质夹杂物的形成。然而，BMAA引起的神经病理学的潜在机制仍然是难以捉摸的。成像质谱是一种强有力的空间查询生物组织中的生化分布的方法，具有高度的化学特异性。因此，本研究的目的是使用基质辅助激光解吸/电离（MALDI）和飞行时间西姆斯（ToF-SIMS成像）表征BMAA诱导的成年大鼠海马病变的脂质微环境。多模态成像通过海马结构的ToF-SIMS扫描进行，然后使用MALDI成像进行全组织扫描。对西姆斯数据进行多变量分析，以描绘病变周围的空间生物化学。数据显示磷脂酰胆碱片段的病变特异性定位，表明神经炎性胶质细胞活化。补充MALDI成像数据显示磷酸乙醇胺水平增加与蛋白质病变共定位，指向与神经毒素诱导的蛋白质积累相关的巨自噬机制。多模式IMS通过ToF-SIMS和MALDI质谱被证明是一个强大的技术，用于神经毒理学研究。
The environmental toxin β-N-methylamino-L-alanine (BMAA) has been causatively linked to neurodegenerative disease pathology. In a rat model, neonatal BMAA exposure resulted in selective uptake in the hippocampal formation and caused learning and memory impairments in adult animals. Moreover, high dose neonatal BMAA exposure resulted in formation of protein inclusions in the CA1 region of the adult hippocampus. However the mechanism underlying BMAA induced neuropathology remains elusive. Imaging mass spectrometry is a powerful method for spatial interrogation of biochemical distribution in biological tissue with high chemical specificity. The aim of this study was to therefore characterize the lipid microenvironment of BMAA-induced hippocampal lesions in adult rats using matrix-assisted laser desorption/ionization (MALDI) and time-of-flight SIMS (ToF-SIMS imaging). Multimodal imaging was carried out by ToF-SIMS scans of the hippocampal formation followed by whole tissue scans using MALDI imaging. Multivariate analysis was performed on the SIMS data in order to delineate the spatial biochemistry surrounding the lesions. The data show lesion-specific localization of phosphatidylcholine fragments, suggesting neuroinflammatory glial cell activation. Complementary MALDI imaging data showed increased levels of phosphoethanolamines colocalizing with the proteopathic lesions pointing to macroautophagic mechanisms associated with neurotoxin-induced protein accumulation. Multimodal IMS by means of ToF-SIMS and MALDI mass spectrometry proved to be a powerful technique for neurotoxicological research.
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新生儿暴露于蓝细菌毒素BMAA会诱导成年海马蛋白表达和神经退行性的变化。
DOI：
10.1093/toxsci/kfs241
发表时间：
2012-12
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Karlsson O;Berg AL;Lindström AK;Hanrieder J;Arnerup G;Roman E;Bergquist J;Lindquist NG;Brittebo EB;Andersson M
通讯作者：
Andersson M
影响因子：
2.7
作者：
Karlsson, Oskar;Roman, Erika;Brittebo, Eva B.
通讯作者：
Brittebo, Eva B.
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
48
作者：
Cornett, Dale S.;Reyzer, Michelle L.;Caprioli, Richard M.
通讯作者：
Caprioli, Richard M.
影响因子：
5.4
作者：
Banack SA;Johnson HE;Cheng R;Cox PA
通讯作者：
Cox PA