NR ACPU
AU Choudhuri,R.; Cui,L.; Yong,C.; Bowyer,S.; Klein,R.M.; Welch,K.M.; Berman,N.E.
TI Cortical spreading depression and gene regulation: relevance to migraine.
QU Annals of Neurology 2002 Apr; 51(4): 499-506
PT journal article
AB 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.
MH Anesthetics; Animal; Apolipoproteins E/genetics; Atrial Natriuretic Factor/genetics; Brain/physiology/surgery; Brain Chemistry/genetics; Calcium Channels, L-Type/genetics; Cytokines/genetics; Gene Expression/drug effects/physiology; Glutathione Transferase/genetics; Mice; Migraine/*genetics/*physiopathology; Models, Animal; Neuropeptide Y/genetics; Oligonucleotide Array Sequence Analysis; Prions/genetics; RNA, Messenger/analysis; Receptors, N-Methyl-D-Aspartate/genetics; Reverse Transcriptase Polymerase Chain Reaction; Spreading Cortical Depression/*genetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
SP englisch
PO USA