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Published on: May 4, 2011

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

N Brunello1

  • 1Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy. brunello.nicoletti@unimo.it

Journal of Affective Disorders
|May 4, 2004
PubMed

Insights

Mood stabilizers like valproate (VPA) and lithium may protect brain cells by altering gene expression and inhibiting harmful signaling pathways. This research sheds light on their therapeutic mechanisms in bipolar disorder.

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.

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