Identification of biomarkers associated with migraine with aura.
The diagnosis of migraine can sometimes be difficult because some patients do not fulfill the International Headache Society's criteria for migraine. Hence, an accurate and reliable diagnostic marker for migraine is required. In this study, lymphocytes were used to establish Epstein-Barr virus (EBV)-immortalized lymphoblast cell lines, which were then analyzed using a differential cRNA microarray analysis. The gene expression results were validated using real-time polymerase chain reaction. Gene expression profiling identified 15 genes as being differentially expressed in lymphoblasts originating from patients diagnosed as having migraine with aura (MA). One-fifth of these genes were associated with cytoskeletal proteins. The expressions of seven genes increased significantly by more than 50% of the value in the controls, while the expressions of eight genes decreased significantly by more than 50% of the value in the controls. We also verified that the expression of alpha-fodrin, which was 1 of the 15 genes that were differentially expressed in lymphoblasts originating from patients with MA, increased after cortical spreading depression in an animal model. Thus, alpha-fodrin might play an important role in the pathophysiology of migraine, possibly serving as a migraine biomarker.
Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa 259-1193, Japan. enagata@is.icc.u-tokai.ac.jp
Eiichiro
E
Nagata
Hidenori
H
Hattori
Mamoru
M
Kato
Saiko
S
Ogasawara
Shigeaki
S
Suzuki
Mamoru
M
Shibata
Toshihiko
T
Shimizu
Junichi
J
Hamada
Takashi
T
Osada
Rie
R
Takaoka
Masataka
M
Kuwana
Tatsuhiko
T
Tsunoda
Sadakazu
S
Aiso
Shunya
S
Takizawa
Norihiro
N
Suzuki
Shigeharu
S
Takagi
D000328:Adult; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002492:Central Nervous System Depressants / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D051597:Hippocalcin / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D020325:Migraine with Aura / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D013049:Spectrin
D015415:Biomarkers; D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D051597:Hippocalcin; D008840:Microfilament Proteins; D011189:Potassium Chloride; D012333:RNA, Messenger; D044346:Receptor, Serotonin, 5-HT1D; D013049:Spectrin