Lipidomic analysis of cerebrospinal fluid by mass spectrometry–based methods

Colsch, Benoît; Seyer, Alexandre; Boudah, Samia; Junot, Christophe

doi:10.1007/s10545-014-9798-0

Cited by 18 publications

(7 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipidomic analyses (Colsch et al, 2015) 8-mo-old Cyp2u1 +/+ , Cyp2u1 +/− , and Cyp2u1 −/− mice were killed by CO 2 asphyxiation, and the cerebral cortices were immediately dissected and frozen in isopentane. Samples were extracted according to a modified Folch method (Folch et al, 1957).…”

Section: Histologic and Immunohistochemical Analysesmentioning

confidence: 99%

Implication of folate deficiency in CYP2U1 loss of function

Pujol

Legrand

Parodi

et al. 2021

Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders. Understanding of their pathogenic mechanisms remains sparse, and therapeutic options are lacking. We characterized a mouse model lacking the Cyp2u1 gene, loss of which is known to be involved in a complex form of these diseases in humans. We showed that this model partially recapitulated the clinical and biochemical phenotypes of patients. Using electron microscopy, lipidomic, and proteomic studies, we identified vitamin B2 as a substrate of the CYP2U1 enzyme, as well as coenzyme Q, neopterin, and IFN-α levels as putative biomarkers in mice and fluids obtained from the largest series of CYP2U1-mutated patients reported so far. We also confirmed brain calcifications as a potential biomarker in patients. Our results suggest that CYP2U1 deficiency disrupts mitochondrial function and impacts proper neurodevelopment, which could be prevented by folate supplementation in our mouse model, followed by a neurodegenerative process altering multiple neuronal and extraneuronal tissues.

show abstract

Section: Histologic and Immunohistochemical Analysesmentioning

confidence: 99%

Implication of folate deficiency in CYP2U1 loss of function

Pujol

Legrand

Parodi

et al. 2021

Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…From bioanalytical point of view, CSF is a challenging biological fluid due to its low 15 µg/mL total lipid content 17 , which is approximately 300-fold lower than that of plasma 12 , 17 . The development of high sensitivity mass spectrometry-based approaches 18 enabled the examination of the CSF lipidome 19 . However, insofar reports focused mainly on dementia 20 – 22 , and comprehensive CSF lipidomic reports dealing with MS and GBS are few and incomplete.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Péter

Török

Petrovics-Balog

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

show abstract

“…This represents about 0.2 % of serum total lipid content (Irani 2009 ) with a huge heterogeneity of lipid species. For this reason, very few lipidomic studies have been conducted on CSF and most of them have been achieved using targeted methods focused on selected lipid families (Colsch et al 2015 ), such as free fatty acids and their derivatives (Farias et al 2011 ; Fonteh et al 2014 ), glycerophospholipids, sphingomyelins, sterols (Tourtellotte 1959 ; Illingworth and Glover 1971 ) and phospholipid families (Mudler et al 2003 ; Kosicek et al 2010 ; Kosicek et al 2012 ; Fonteh et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Annotation of the human cerebrospinal fluid lipidome using high resolution mass spectrometry and a dedicated data processing workflow

Seyer¹,

Boudah

Broudin³

et al. 2016

Metabolomics

Self Cite

View full text Add to dashboard Cite

IntroductionDue to its proximity with the brain, cerebrospinal fluid (CSF) could be a medium of choice for the discovery of biomarkers of neurological and psychiatric diseases using untargeted analytical approaches.ObjectivesThis study explored the CSF lipidome in order to generate a robust mass spectral database using an untargeted lipidomic approach.MethodsCerebrospinal fluid samples from 45 individuals were analyzed by liquid chromatography coupled to high-resolution mass spectrometry method (LC-HRMS). A dedicated data processing workflow was implemented using XCMS software and adapted filters to select reliable features. In addition, an automatic annotation using an in silico lipid database and several MS/MS experiments were performed to identify CSF lipid species.ResultsUsing this complete workflow, 771 analytically relevant monoisotopic lipid species corresponding to 550 unique lipids which represent five major lipid families (i.e., free fatty acids, sphingolipids, glycerophospholipids, glycerolipids, and sterol lipids) were detected and annotated. In addition, MS/MS experiments enabled to improve the annotation of 304 lipid species. Thanks to LC-HRMS, it was possible to discriminate between isobaric and also isomeric lipid species; and interestingly, our study showed that isobaric ions represent about 50 % of the total annotated lipid species in the human CSF.ConclusionThis work provides an extensive LC/HRMS database of the human CSF lipidome which constitutes a relevant foundation for future studies aimed at finding biomarkers of neurological disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1023-8) contains supplementary material, which is available to authorized users.

show abstract

Lipidomic analysis of cerebrospinal fluid by mass spectrometry–based methods

Cited by 18 publications

References 129 publications

Implication of folate deficiency in CYP2U1 loss of function

Implication of folate deficiency in CYP2U1 loss of function

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Annotation of the human cerebrospinal fluid lipidome using high resolution mass spectrometry and a dedicated data processing workflow

Contact Info

Product

Resources

About