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Metabolic profiling for the identification of Huntington biomarkers by on‐line solid‐phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools
Author(s) -
Pont Laura,
Benavente Fernando,
Jaumot Joaquim,
Tauler Romà,
Alberch Jordi,
Ginés Silvia,
Barbosa José,
SanzNebot Victoria
Publication year - 2016
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201500378
Subject(s) - mass spectrometry , capillary electrophoresis , chromatography , solid phase extraction , chemistry , capillary electrophoresis–mass spectrometry , profiling (computer programming) , computational biology , biology , computer science , electrospray ionization , operating system
In this work, an untargeted metabolomic approach based on sensitive analysis by on‐line solid‐phase extraction capillary electrophoresis mass spectrometry (SPE‐CE‐MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild‐type (wt) and HD (R6/1) mice of different ages (8, 12, and 30 weeks), were analyzed by C 18 ‐SPE‐CE‐MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR‐ALS) was applied to the multiple full scan MS datasets. This strategy permitted the resolution of a large number of metabolites being characterized by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow‐up the HD progression. The intracellular signaling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors, and changed expression of neurotransmitters.