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Oral Sessions
Day 3, June 24(Tue.) 11:55-12:10
Room B (Maesato Center)
- 3B-O1-1155
Fully automated surface lipidomics by LC/differential ion mobility spectrometry/MS reveals alteration of brain lipid metabolism in prodromal Parkinson's disease model mice
(1Juntendo Univ., 2RIKEN, 3Kyoto Univ.)
oHisako Akiyama1,2, Keiko Fukasawa1,2, Tomoyuki Taguchi3, Masashi Ikuno3, Hodaka Yamakado3, Peter Greimel2, Ryosuke Takahashi3, Nobutaka Hattori1,2, Hiroyuki Kamiguchi2
Glucosylceramide (GlcCer) is degraded by β-glucocerebrosidase (GBA). Heterozygous mutations in lysosomal GBA (GBA1) gene are the most potent risk factor for Parkinson's disease (PD). GBA1 heterozygous mutations reduce not only GBA1 activity but also non-lysosomal GBA (GBA2) activity. Previously, we demonstrated an existence of sterylglycosides (SGs) in vertebrate brain for the first time. We demonstrated that GBA1 and GBA2 possess not only GlcCer hydrolase activity but also SG synthesizing and degrading activities. To elucidate the involvement of SGs in PD, it is important to understand the spatial distribution of SGs in brain. In this study, we developed an analytical platform for analyzing the spatial distribution of SGs in tissue samples by MS. Since SGs include isobaric isomers, differential mobility spectrometry (DMS) was exploited for the separation of SGs. By combination of LC/DMS/MS and robotic liquid extraction surface analysis which enables lipid extraction from the surface of multiple regions of a tissue section using organic solvent, we established a new analytical platform which enables fully-automated series of operations from lipid extraction to detection of isomeric lipids. Using this new platform, we analyzed brains from prodromal PD model mice and revealed alteration of brain lipid metabolism compared to that in wild type mice.