Cortical spreading depression and gene regulation: relevance to migraine.
Version of Record online: 27 MAR 2003
Headache: The Journal of Head and Face Pain
Volume 43, Issue 4, page 427, April 2003
How to Cite
Choudhuri, R., Cui, L. and C et al., Y. (2003), Cortical spreading depression and gene regulation: relevance to migraine. Headache: The Journal of Head and Face Pain, 43: 427. doi: 10.1046/j.1526-4610.2003.03085_12.x
- Issue online: 27 MAR 2003
- Version of Record online: 27 MAR 2003
- Cited By
Ann Neurol. 2002;51:499-506.
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 300 mM 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 1180 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.
Comment: Dr. Welch's group is systematically searching for gene expression targets which may lead to improvement both in understanding migraine at a molecular level and in development of new treatment strategies. SJT