Plasma metabolic profiling after cortical spreading depression in a transgenic mouse model of hemiplegic migraine by capillary electrophoresis--mass spectrometry.

Abstract:

:Migraine is a common brain disorder characterized by recurrent attacks of severe headaches and other neurological symptoms. In one-third of patients headaches are accompanied by auras, which consist of transient visual and sensory disturbances, believed to be caused by cortical spreading depression (CSD). CSD is characterized by a wave of neuronal and glial depolarization with concomitant changes in metabolite concentrations in the brain and cerebrospinal fluid. It remains unknown whether CSD-induced brain metabolic changes can be captured outside the central nervous system, i.e., in peripheral fluids. This study investigated plasma metabolic changes in transgenic mice that harbor a gene mutation in voltage-gated CaV2.1 Ca(2+) channels previously identified in patients with familial hemiplegic migraine, a subtype of migraine with auras. The use of a mouse model allows investigation of molecular changes occurring shortly after CSD, which is notoriously difficult in patients. Capillary electrophoresis - mass spectrometry was used for the analysis of plasma samples to obtain, for the first time, a comprehensive view of molecular changes immediately after experimentally induced CSD. Multivariate data analysis showed a clear distinction between profiles of transgenic and wild-type animals after CSD. Two metabolites considered important for this discrimination were tentatively identified as being lysine and its by-product pipecolic acid with additional evidence provided by hydrophilic interaction chromatography combined with tandem mass spectrometry. The changed metabolites suggest a compensatory increase in GABAergic neurotransmission upon enhanced excitatory neurotransmission. These results show that CSD induces metabolic remodeling in transgenic migraine mice that can be captured and measured in plasma.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Shyti R,Kohler I,Schoenmaker B,Derks RJ,Ferrari MD,Tolner EA,Mayboroda OA,van den Maagdenberg AM

doi

10.1039/c5mb00049a

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1462-71

issue

5

eissn

1742-206X

issn

1742-2051

journal_volume

11

pub_type

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