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The Role of Glutathione Metabolism in the Neuroprotective Effect of Mood Stabilizers

Several lines of evidence implicate oxidative stress in the pathophysiology of bipolar disorder (BPD). The mood stabilizers lithium and valproate have been shown to protect against oxidative stress-induced cell death. This study examined whether an increase in cellular reductive potential due to glutathione (GSH) synthesis up-regulation underlies this neuroprotective effect. Using primary rat cortical neurons as a model, this study demonstrated that unlike lithium and valproate, carbamazepine and lamotrigine do not exert neuroprotective effects against H2O2-induced cell death. Moreover, the level of GSH and the GSH:GSSG ratio in neurons and in rat brain remained unchanged following chronic treatment with either lithium or valproate. Similarly, this study did not find a significant effect of treatment on the expression of genes encoding γ-glutamylcysteine ligase sub-units, Gclc and Gclm, in both neurons and the rat brain. These findings suggest that other molecular targets of lithium and valproate likely mediate the observed neuroprotective effects.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25888
Date13 January 2011
CreatorsPasiliao, Clarissa
ContributorsLi, Peter, Warsh, Jerry
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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