Proteomic serum profile of female migraineurs

Background: Migraine is considered a complex disease, a variable disorder of nervous system function that has a genetic background, yet the final phenotypic outcome largely depends on the individual’s environment and lifestyle. In particular, there is a clear relationship between menstruation cycle and the onset of migraine. In fact, over 50% of migraine women suffer from perimenstrual attacks, that are more serious, lasting and resistant to the treatment than non-menstrual migraine attacks [1]. We hypothesized that serum proteome analysis could help to identify potential biomarkers of menstrually-related migraine (MM) and post-menopausal migraine (PMM). Methods: We analyzed and compared the serum proteomic profile of three groups: women suffering from MM (n=15), post-menopausal women suffering from migraine without aura (n=15) and non-headache control females (n=14). The enrolled migraineurs were patients afferent to the Headache Centre of Modena University Hospital; the control females were friends or relatives of the above patients. All women gave their written consent and the Ethical Committee of Modena approved the study. Serum samples obtained from each study participant were subjected to bi-dimensional gel electrophoresis (2-DE) coupled to mass spectrometry (MS) analysis for protein identification. The 2D-gel maps were examined by the PDQuest software, to detect the differentially expressed protein spots between the different groups [2]. Results: A total of 13 significantly different protein spots were revealed in migraine women compared to controls. Of these proteins, most (n=10) resulted increased in migraineurs vs controls, while only 3 proteins were decreased. Specifically, the greater expression differences involved the up-regulation of transthyretin in PMM and the down-regulation of apolipoprotein A1 in MM. Other proteins, such as prothrombin, serum amyloid P-component and Ig-k-chain C region, were found significantly over-expressed in migraine sufferers in comparison to controls, while one spot, recognized as serum amyloid A-4 protein, resulted decreased. Conclusion: The serum proteome of migraine women showed proteins characteristic of cell damage, oxidative stress and lipoperoxidation, as well as acute phase proteins and inflammation markers. This pilot study demonstrates the ability of proteomics to reveal differences in protein expression between women suffering from MM and post-menopausal women suffering from migraine without aura against non-headache women. Further analysis will be carried out to expand and confirm these preliminary results. [1] Calhoun A.H. Headache 2018; 58:626-630. [2] Bellei E., et al. Amino Acids 2011; 40:145-156.