TY - JOUR
T1 - Role of glycogen synthase kinase-3β in early depressive behavior induced by mild traumatic brain injury
AU - Shapira, Moran
AU - Licht, Avital
AU - Milman, Anat
AU - Pick, Chaim G.
AU - Shohami, Esther
AU - Eldar-Finkelman, Hagit
PY - 2007/4
Y1 - 2007/4
N2 - Traumatic brain injury (TBI) is a triggering event for a set of pathophysiological changes and concomitant depressive behavior. Glycogen synthase kinase-3 (GSK-3) is a potent in vivo regulator of cell apoptosis and, in addition, is implicated in depressive behavior. In this study, we investigated the role of GSK-3 in the physiological model of mild TBI (mTBI) at both the cellular and behavior levels. mTBI resulted in increased phosphorylation of inhibitory site serine9 of GSK-3β, which coincided with increased serine473 phosphorylation of its upstream kinase PKB and accumulation of its downstream target β-catenin in the hippocampus. mTBI induced a depressive behavior which was evident as early as 24 h post-injury. Pretreatment with GSK-3 inhibitors, lithium, or L803-mts prevented mTBI-induced depression. We suggest that mTBI elicits a pro-survival cascade of PKB/GSK-3β/β-catenin as part of a rehabilitation program. Furthermore, the use of selective GSK-3 inhibitors may have therapeutic benefits in treatment conditions associated with brain injury.
AB - Traumatic brain injury (TBI) is a triggering event for a set of pathophysiological changes and concomitant depressive behavior. Glycogen synthase kinase-3 (GSK-3) is a potent in vivo regulator of cell apoptosis and, in addition, is implicated in depressive behavior. In this study, we investigated the role of GSK-3 in the physiological model of mild TBI (mTBI) at both the cellular and behavior levels. mTBI resulted in increased phosphorylation of inhibitory site serine9 of GSK-3β, which coincided with increased serine473 phosphorylation of its upstream kinase PKB and accumulation of its downstream target β-catenin in the hippocampus. mTBI induced a depressive behavior which was evident as early as 24 h post-injury. Pretreatment with GSK-3 inhibitors, lithium, or L803-mts prevented mTBI-induced depression. We suggest that mTBI elicits a pro-survival cascade of PKB/GSK-3β/β-catenin as part of a rehabilitation program. Furthermore, the use of selective GSK-3 inhibitors may have therapeutic benefits in treatment conditions associated with brain injury.
UR - http://www.scopus.com/inward/record.url?scp=33947603193&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2006.12.006
DO - 10.1016/j.mcn.2006.12.006
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C2 - 17289399
AN - SCOPUS:33947603193
SN - 1044-7431
VL - 34
SP - 571
EP - 577
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 4
ER -