AUTHOR=Khaiboullina Svetlana F. , Mendelevich Elena G. , Shigapova Leyla H. , Shagimardanova Elena , Gazizova Guzel , Nikitin Alexey , Martynova Ekaterina , Davidyuk Yuriy N. , Bogdanov Enver I. , Gusev Oleg , van den Maagdenberg Arn M. J. M. , Giniatullin Rashid A. , Rizvanov Albert A. 

TITLE=Cerebellar Atrophy and Changes in Cytokines Associated with the CACNA1A R583Q Mutation in a Russian Familial Hemiplegic Migraine Type 1 Family

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00263

DOI=10.3389/fncel.2017.00263

ISSN=1662-5102

ABSTRACT=<p><bold>Background:</bold> Immune mechanisms recently emerged as important contributors to migraine pathology with cytokines affecting neuronal excitation. Therefore, elucidating the profile of cytokines activated in various forms of migraine, including those with a known genetic cause, can help in diagnostic and therapeutic approaches.</p><p><bold>Methods:</bold> Here we (i) performed exome sequencing to identify the causal gene mutation and (ii) measured, using Bio-Plex technology, 22 cytokines in serum of patients with familial migraine (two with hemiplegic migraine and two with migraine with aura) from a Russian family that ethnically belongs to the Tatar population. MRI scanning was used to assess cerebellar atrophy associated with migraine in mutation carriers.</p><p><bold>Results:</bold> Whole-exome sequencing revealed the R583Q missense mutation in the <italic>CACNA1A</italic> gene in the two patients with hemiplegic migraine and cerebellar ataxia with atrophy, confirming a FHM1 disorder. Two further patients did not have the mutation and suffered from migraine with aura. Elevated serum levels of pro-inflammatory and pro-nociceptive IL-6 and IL-18 were found in all four patients (compared to a reference panel), whereas pro-apoptotic SCGF-β and TRAIL were higher only in the patients with the FHM1 mutation. Also, cytokines CXCL1, HGF, LIF, and MIF were found particularly high in the two mutation carriers, suggesting a possible role of vascular impairment and neuroinflammation in disease pathogenesis. Notably, some “algesic” cytokines, such as β-NGF and TNFβ, remained unchanged or even were down-regulated.</p><p><bold>Conclusion:</bold> We present a detailed genetic, neurological, and biochemical characterization of a small Russian FHM1 family and revealed evidence for higher levels of specific cytokines in migraine patients that support migraine-associated neuroinflammation in the pathology of migraine.</p>