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Cortical spreading depression and gene regulation: Relevance to migraine
Author(s) -
Choudhuri Rajani,
Cui MD Lisa,
Yong Chi,
Bowyer Susan,
Klein Robert M.,
Welch MD K. M. A.,
Berman Nancy E. J.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10158
Subject(s) - cortical spreading depression , migraine , neuropeptide , calcitonin gene related peptide , gene , medicine , gene expression , endocrinology , neuropeptide y receptor , biology , downregulation and upregulation , neuroscience , receptor , genetics
Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5‐minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase–polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione‐S‐transferase‐5, and apolipoprotein E). L‐type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes.