Depression Research Today is a free monthly online journal that collates and summarizes the latest research about Depression, including details on clinical depression, medication, symptoms, treatment, counselling, therapy.

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

Shapira M, Licht A, Milman A, Pick CG, Shohami E, Eldar-Finkelman H

Department of Molecular Human Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.

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 serine(9) of GSK-3beta, which coincided with increased serine(473) phosphorylation of its upstream kinase PKB and accumulation of its downstream target beta-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-3beta/beta-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.

Published 2 April 2007 in Mol Cell Neurosci, 34(4): 571-7.
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