Identification of biomarkers associated with migraine with aura

Nagata, Eiichiro; Hattori, Hidenori; Kato, Mamoru; Ogasawara, Saiko; Suzuki, Shigeaki; Shibata, Mamoru; Shimizu, Toshihiko; Hamada, Junichi; Osada, Takashi; Takaoka, Rie; Kuwana, Masataka; Tsunoda, Tatsuhiko; Aiso, Sadakazu; Takizawa, Shunya; Suzuki, Norihiro; Takagi, Shigeharu

doi:10.1016/j.neures.2009.02.001

Cited by 14 publications

(12 citation statements)

References 32 publications

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“…Other findings regarding lymphocytes include lower β‐adrenergic receptor sensitivity 35 and enhanced dopamine D5‐receptor expression 36 . Recently, Nagata et al demonstrated that lymphoblasts derived from migraine patients exhibited higher serotonin levels relative to controls, 37 as well as increased expression of some genes, particularly the α‐fodrin gene, a cytoskeletal protein abundantly expressed in the brain and linked to the cortical spreading depression, while the contrary was observed for other genes 38 . Abnormal functioning of Na/K ATPase, an enzyme linked to cortical spreading depression, in lymphocytes from patients with migraine with aura was also reported 39 .…”

Section: Commentsmentioning

confidence: 99%

Analysis of Leukocytes in Medication-Overuse Headache, Chronic Migraine, and Episodic Migraine

Forcelini

Dantas

Luz

et al. 2011

Headache: The Journal of Head and Face Pain

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Section: Commentsmentioning

confidence: 99%

Analysis of Leukocytes in Medication-Overuse Headache, Chronic Migraine, and Episodic Migraine

Forcelini

Dantas

Luz

et al. 2011

Headache: The Journal of Head and Face Pain

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“…ACE deletion polymorphisms are more common in patients with migraine [ 11 ]. Moreover, the levels of α-fodrin mRNA, which encodes a cytoskeletal protein, are increased in MA [ 12 ]. However, the above-mentioned results have not been fully validated.…”

Section: Introductionmentioning

confidence: 99%

Serum apolipoprotein E may be a novel biomarker of migraine

Yuasa¹,

Nagata

Fujii

et al. 2018

PLoS ONE

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Migraine attacks alter various molecules that might be related to the pathophysiology of migraine, such as serotonin, calcitonin gene-related peptide, and nitric oxide. The underlying pathophysiology of migraine is as yet unclear. We explored key proteins related to the pathogenesis of migraine here. Serum was collected from two patients with migraine with aura (MA) and seven patients with migraine without aura (MO) during attack-free periods and migraine attacks. Samples were analyzed using 2-dimensional gel electrophoresis. Nineteen protein spots were altered between the attack-free versus migraine attack periods. Mass spectrometric analysis was performed to identify the proteins within each of the 19 altered spots. Thirty-six proteins were significantly altered in samples collected during attack-free periods versus migraine attacks. The protein with the statistically most significant MASCOT/Mowse score (268±112) among lipoproteins was apolipoprotein (ApoE). In the MA and MO groups, ApoE protein levels were significantly higher during migraine attack than during the attack-free period (p<0.05). ApoE protein levels were also significantly increased in the MA group during the attack-free period compared to healthy controls and patients with tension type headaches (p<0.01). Migraine alters ApoE levels, especially in MA. ApoE might play an important role in the pathophysiology of migraine, and may act as a diagnostic biomarker of migraine.

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“…For migraine, no gene expression data from disease-conditions are available. Few gene expression profiling studies have been carried out for migraine, i.e., in whole blood of episodic and chronic migraine patients (Hershey et al 2004 ) and menstrual migraine patients (Hershey et al 2012 ), in immortalised cell lines of migraine with aura patients (Nagata et al 2009 ), and in brain material of transgenic KI FHM1 mice (de Vries et al 2014 ), but no overlapping deregulated genes or pathways have been identified. Nor is there a large set of causal genes, except for three genes ( CACNA1A, ATP1A2 and SCN1A ) (De Fusco et al 2003 ; Dichgans et al 2005 ; Ophoff et al 1996 ) that have been identified for FHM, that can guide gene identification efforts in the common forms of migraine.…”

Section: Introductionmentioning

confidence: 99%

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas

et al. 2016

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Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1638-x) contains supplementary material, which is available to authorized users.

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Identification of biomarkers associated with migraine with aura

Cited by 14 publications

References 32 publications

Analysis of Leukocytes in Medication-Overuse Headache, Chronic Migraine, and Episodic Migraine

Analysis of Leukocytes in Medication-Overuse Headache, Chronic Migraine, and Episodic Migraine

Serum apolipoprotein E may be a novel biomarker of migraine

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas

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