Cortical spreading depression and gene regulation: relevance to migraine.
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.
Choudhuri
Rajani
R
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Cui
Lisa
L
Yong
Chi
C
Bowyer
Susan
S
Klein
Robert M
RM
Welch
K M A
KM
Berman
Nancy E J
NE
D000777:Anesthetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001921:Brain / Q000502:physiology / Q000601:surgery; D001923:Brain Chemistry / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics; D013181:Cortical Spreading Depression / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics; D051379:Mice; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology*; D023421:Models, Animal; D009478:Neuropeptide Y / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011328:Prions / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000777:Anesthetics; D001057:Apolipoproteins E; D009320:Atrial Natriuretic Factor; D020746:Calcium Channels, L-Type; D016207:Cytokines; D005982:Glutathione Transferase; D009478:Neuropeptide Y; D011328:Prions; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate