Mild hypothermia decreases GSK3beta expression following global cerebral ischemia.
BACKGROUND
The serine/threonine kinase glycogen synthase kinase 3beta (GSK3beta) is abundant in the central nervous system and is neuron-specific. GSK3beta plays a pivotal role in the regulation of numerous cellular functions (including phosphorylation) and, thereby, regulation of many metabolic, signaling, and structural proteins as well as transcription factors that can influence cell survival. This article reports that GSK3beta expression following global cerebral ischemia (GCI) is altered by the neuroprotectant, mild hypothermia (33 degrees C).


METHODS
Male Sprague-Dawley rats were anesthetized and subjected to GCI; arterial blood pressure was reduced to 30 mmHg by blood withdrawal via the jugular vein, and both common carotid arteries were occluded with aneurysm clips for 8 minutes. Hypothermia (33 degrees C) was induced in half the rats 10 minutes prior to GCI and was maintained for 3 hours. Rats were killed 24 or 72 hours later to assess cell death and GSK3beta expression.


RESULTS
At 72 hours post-GCI, levels of GSK3beta expression were significantly lower in hypothermic rats than in normothermic rats. This reduction in GSK3beta correlated with marked neuroprotection and reduced terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining in hippocampal CA1 neurons. No significant changes in phosphorylated GSK3beta expression were observed.


CONCLUSIONS
These data suggest that GSK3beta plays a role in GCI pathology that can be altered by mild hypothermia.
Kelly
Stephen
S
Department of Neurosurgery, Stanford University, Stanford, CA 94121, USA.
Cheng
Danye
D
Steinberg
Gary K
GK
Yenari
Midori A
MA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000628:therapy*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3