scholarly journals Characteristics of cortical spreading depression and c-Fos expression in transgenic mice having a mutation associated with familial hemiplegic migraine 2

Cephalalgia ◽  
2020 ◽  
Vol 40 (11) ◽  
pp. 1177-1190
Author(s):  
Chunhua Tang ◽  
Miyuki Unekawa ◽  
Mamoru Shibata ◽  
Yutaka Tomita ◽  
Yoshikane Izawa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Orthologous Gene ◽  
Underlying Mechanism ◽  
Familial Hemiplegic Migraine ◽  
Wild Type ◽  
Hemiplegic Migraine ◽  
Fos Expression

Background Cortical spreading depression is thought to be the underlying mechanism of migraine aura. In 2006, three relatives having the point mutation E700K in ATP1A2 exon 15 were diagnosed with familial hemiplegic migraine 2 characterized by complicated forms of aura. Here, we generated a transgenic mouse model having the human E700K mutation in the Atp1a2 orthologous gene. Objective To investigate the characteristics of cortical spreading depression in a mouse model with E700K mutation in the Atp1a2. Methods Cortical spreading depression was induced by applying stepwise increases of KCl concentration or electrical stimulation intensity to C57BL/6J-Tg(Atp1a2*E700K)9151Kwk mice (Tg, both sexes) and corresponding wild-type animals. Under urethane anesthesia, the responsiveness and threshold to cortical spreading depression were examined and the distribution of c-Fos expression, a neuronal activity marker, was immunohistochemically determined. Results Overall, Tg mice showed significantly faster propagation velocity ( p < 0.01) and longer full-width-at-half-maximum ( p < 0.01) than wild-type animals, representing a slower recovery from direct current potential deflection. The cortical spreading depression threshold tended to be lower in Tg, especially in females. c-Fos-positive cells were significantly enhanced in the ipsilateral somatosensory cortex, piriform cortex, amygdala and striatum (each p < 0.05 vs. contralateral side). Numbers of c-Fos positive cells were significantly higher in the ipsilateral amygdala of Tg, as compared with wild-type animals ( p < 0.01). Conclusion The effect of cortical spreading depression may be greater in E700K transgenic mice than that in wild-type animals, while the threshold for cortical spreading depression shows little change. Higher c-Fos expression in the amygdala may indicate alterations of the limbic system in Tg, suggesting an enhanced linkage between cortical spreading depression and amygdala connectivity in familial hemiplegic migraine 2 patients.

scholarly journals Increased Susceptibility to Cortical Spreading Depression in the Mouse Model of Familial Hemiplegic Migraine Type 2

PLoS Genetics ◽  
2011 ◽  
Vol 7 (6) ◽  
pp. e1002129 ◽  
Author(s):  
Loredana Leo ◽  
Lisa Gherardini ◽  
Virginia Barone ◽  
Maurizio De Fusco ◽  
Daniela Pietrobon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Increased Susceptibility

Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice

2015 ◽  
Vol 263 ◽  
pp. 214-220 ◽  
Author(s):  
Reinald Shyti ◽  
Katharina Eikermann-Haerter ◽  
Sandra H. van Heiningen ◽  
Onno C. Meijer ◽  
Cenk Ayata ◽  
...  
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Familial Hemiplegic Migraine ◽  
Mutant Mice ◽  
Stress Hormone ◽  
Hemiplegic Migraine

Enhanced susceptibility to cortical spreading depression in two types of Na+,K+-ATPase α2 subunit-deficient mice as a model of familial hemiplegic migraine 2

Cephalalgia ◽  
2017 ◽  
Vol 38 (9) ◽  
pp. 1515-1524 ◽  
Author(s):  
Miyuki Unekawa ◽  
Keiko Ikeda ◽  
Yutaka Tomita ◽  
Kiyoshi Kawakami ◽  
Norihiro Suzuki
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Propagation Rate ◽  
Familial Hemiplegic Migraine ◽  
High Dose ◽  
High Susceptibility ◽  
Hemiplegic Migraine ◽  
Gene Encoding ◽  
Significant Difference ◽  
The Difference

Background Patients with familial hemiplegic migraine type 2 (FHM2) have a mutated ATP1A2 gene (encoding Na+,K+-ATPase α2 subunit) and show prolonged migraine aura. Cortical spreading depression (CSD), which involves mass depolarization of neurons and astrocytes that propagates slowly through the gray matter, is profoundly related to aura. Methods In two types of Atp1a2-defective heterozygous mice, Atp1a2tm1Kwk (C-KO) and Atp1a2tm2Kwk (N-KO), the sensitivity and responsiveness to CSD were examined under urethane anesthesia. Results In both cases, heterozygotes exhibited a low threshold for induction of CSD, faster propagation rate, slower recovery from DC deflection, and profound suppression of the electroencephalogram, compared to wild-type mice. A high dose of KCl elicited repeated CSDs for a longer period, with a tendency for a greater frequency of CSD occurrence in heterozygotes. The difference of every endpoint was slightly greater in N-KO than C-KO. Change of regional cerebral blood flow in response to CSD showed no significant difference. Conclusion Heterozygotes of Atp1a2-defective mice simulating FHM2 demonstrated high susceptibility to CSD rather than cortical vasoreactivity, and these effects may differ depending upon the knockout strategy for the gene disruption. These results suggest that patients with FHM2 may exhibit high susceptibility to CSD, resulting in migraine.

Plasma metabolic profiling after cortical spreading depression in a transgenic mouse model of hemiplegic migraine by capillary electrophoresis – mass spectrometry

2015 ◽  
Vol 11 (5) ◽  
pp. 1462-1471 ◽  
Author(s):  
Reinald Shyti ◽  
Isabelle Kohler ◽  
Bart Schoenmaker ◽  
Rico J. E. Derks ◽  
Michel D. Ferrari ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Capillary Electrophoresis ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Metabolic Profiling ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Transgenic Mouse Model ◽  
Metabolic Changes ◽  
Hemiplegic Migraine

Cortical spreading depression-induced brain metabolic changes have been captured in the plasma of a transgenic migraine mouse model using CE-MS.

scholarly journals Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine

2019 ◽  
Vol 9 (7) ◽  
pp. 172 ◽  
Author(s):  
Salvo Lombardo ◽  
Emanuela Mazzon ◽  
Maria Basile ◽  
Eugenio Cavalli ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Mouse Model ◽  
Receptor Antagonist ◽  
Spreading Depression ◽  
Occipital Cortex ◽  
Familial Hemiplegic Migraine ◽  
Therapeutic Strategies ◽  
Hemiplegic Migraine ◽  
Inflammatory Genes ◽  
Glial Depolarization

Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave of neuronal and glial depolarization originating in the occipital cortex, followed by temporary neuronal silencing. During a migraine attack, increased expression of inflammatory mediators, along with a decrease in the expression of anti-inflammatory genes, have been observed. The aim of this study was to evaluate the expression of inflammatory genes, in particular that of IL-1 receptor antagonist (IL-1RN), following CSD in a mouse model of familial hemiplegic migraine type 1 (FHM-1). We show here that the expression of IL-1RN was upregulated after the CSD, suggesting a possible attempt to modulate the inflammatory response. This study allows researchers to better understand the development of the disease and aids in the search for new therapeutic strategies in migraine.

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