Role of glycogen synthase kinase-3β  in early depressive behavior induced by mild traumatic brain injury

详细信息    查看全文

• 作者：Moran Shapira ; Avital Licht ; Anat Milman ; Chaim G. Pick ; Esther Shohami ; Hagit Eldar-Finkelman
• 刊名：Molecular and Cellular Neuroscience
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：34
• 期：4
• 页码：571-577
• 全文大小：729 K

文摘

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.