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

Frontiers in Cellular Neuroscience

Guzel Gazizova¹  Albert A. Rizvanov¹  Leyla H. Shigapova¹  Ekaterina Martynova¹  Yuriy N. Davidyuk¹  Svetlana F. Khaiboullina¹  Elena Shagimardanova¹  Rashid A. Giniatullin²  Enver I. Bogdanov³  Elena G. Mendelevich³  Arn M. J. M. van den Maagdenberg⁴  Alexey Nikitin⁵  Oleg Gusev⁷ 

[1] Department of Genetics, Institute of Fundamental Medicine and Biology, Kazan Federal UniversityKazan, Russia;Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandKuopio, Finland;Department of Neurology, Kazan State Medical UniversityKazan, Russia;Departments of Human Genetics and Neurology, Leiden University Medical CenterLeiden, Netherlands;Federal Research and Clinical Center, Federal Medical-Biological Agency of RussiaMoscow, Russia;Innovation Center, RIKENYokohama, Japan;Preventive Medicine and Diagnosis Innovation Program, RIKENYokohama, Japan;

关键词: migraine;    FHM1;    cytokines;    inflammation;    nociception;   

DOI  :  10.3389/fncel.2017.00263

来源: DOAJ

【 摘 要 】

Background: 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.Methods: 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.Results: Whole-exome sequencing revealed the R583Q missense mutation in the CACNA1A 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.Conclusion: 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.

【 授权许可】

Unknown