Mood stabilizers: protecting the mood...protecting the brain

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• The precise mechanisms of mood stabilizers in bipolar disorder remain unclear.
• Anticonvulsants like valproate (VPA) show efficacy, suggesting shared pathways with lithium.
• Research focuses on VPA and lithium's effects on cellular signaling, including cyclic AMP and phosphoinositide pathways.

Purpose of the Study:

• To investigate the molecular mechanisms of mood stabilizers, specifically valproate (VPA) and lithium.
• To explore their impact on cellular signal transduction and genomic alterations.
• To understand how these drugs may prevent neuronal degeneration in bipolar disorder.

Main Methods:

• Analysis of cellular signal transduction systems, including protein kinase C (PKC) pathways.
• Examination of genomic alterations and gene expression, particularly early inducible genes like AP-1.
• Assessment of effects on anti-apoptotic protein bcl-2 and GSK-3 beta activity.

Main Results:

• VPA and lithium affect the protein kinase C (PKC) signaling pathway, similar to lithium but largely independent of myo-inositol.
• Prolonged administration suggests genomic-level changes, including altered expression of AP-1 transcription factors.
• Both VPA and lithium stimulate bcl-2 expression and inhibit GSK-3 beta, enhancing cellular resistance to apoptosis.

Conclusions:

• Mood stabilizers may restore balance in aberrant brain signaling pathways.
• They appear to prevent neuronal degeneration by upregulating cytoprotective proteins like bcl-2.
• These findings provide insight into the neuroprotective effects of VPA and lithium in bipolar disorder treatment.