Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain.
Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3beta and GSK3alpha, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with approximately 90% dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3beta and GSK3alpha in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3.
Li
Xiaohua
X
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 1720 7th Avenue South, Birmingham, AL 35294-0017, USA.
Friedman
Ari B
AB
Roh
Myoung-Sun
MS
Jope
Richard S
RS
D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002697:Chloral Hydrate / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010424:Pentobarbital / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011180:Postmortem Changes; D012694:Serine / Q000378:metabolism*; D013997:Time Factors
D000777:Anesthetics; D007527:Isoenzymes; D002697:Chloral Hydrate; D012694:Serine; D038362:Glycogen Synthase Kinase 3; D010424:Pentobarbital; D006221:Halothane