Objective: Lipidomic analysis of mice with spinocerebellar ataxia by mass spectrometry.

Background: Ataxia is a movement disorder affecting balance and coordination of limbs, gait, eyes and speech. Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominantly inherited neurodegenerative disorder for which there is no available disease modifying treatment or cure. Lipid profiling (lipidomics) in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s recently suggest that there are lipid anomalies associated with a wide spectrum of neurodegenerative diseases. Liquid-microjunction surface sampling probe (LMJ-SSP) is an emerging ambient ionization mass spectrometry technique based on the continuous flow of solvent using an in situ micro-extraction device. It provides a unique opportunity to sample thick tissue sections with no prior sample preparation on an ambient platform, whist allowing direct analysis of the metabolic profile related to the disease state. 

Methods: Transgenic SCA1 mice (B05) were sacrificed and whole brains were harvested immediately from the skull fresh, without perfusion. The fresh whole mouse brain was sectioned using a high-grade aluminum alloy 1 mm coronal rodent matrix (ASI Instruments, Warren, MI, USA) immediately post sacrifice. Sections were placed directly onto glass slides and frozen at -80 ºC prior to sampling. The cerebellum of wild type and diseased mice were sampled for 1 minute on a Prosolia FlowprobeTM (Indianapolis, IN, USA). A Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer was used for all experiments. All data were analyzed using MetaboAnalyst.

Results: LMJ-SSP showed good promise for sampling mouse brains. Using MetaboAnalyst, the data was subject to Principal Component Analysis (PCA), an unsupervised multivariate statistical analysis technique. There were distinct differences observed between the wild type and transgenic mice in glycerophospholipids (e.g. phosphatidylcholine) and phospholipids (e.g. sphingomylein) between the two groups. 

Conclusions: To the best of our knowledge, this is the first lipidomic study of the ataxic brain, utilizing FlowProbeTM technology. We detected several significant differences in lipid features in the ataxic brain, suggesting that lipid metabolism is altered in several progressive ataxic conditions. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-the-lipidomic-signature-of-spinocerebellar-ataxia-sca1-using-a-liquid-microjunction-surface-sampling-probe/