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Neurochemical Research

, Volume 34, Issue 3, pp 536–541 | Cite as

Chronic Administration of Mood Stabilizers Upregulates BDNF and Bcl-2 Expression Levels in Rat Frontal Cortex

  • Yunyoung C. Chang
  • Stanley I. Rapoport
  • Jagadeesh S. Rao
Original Paper

Abstract

Brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2) proteins are neuroprotective factors involved in neuronal signaling, survival and plasticity. Both can be regulated by cyclic AMP response element binding (CREB) protein. Decreased levels of BDNF and Bcl-2 are implicated in the pathogenesis of bipolar disorder. The present study investigated whether chronically administered mood stabilizers would increase BDNF and/or Bcl-2 levels in rat brain. Real time RT-PCR, sandwich ELISA and Western blotting were used to measure BDNF and Bcl-2 mRNA and protein levels in the frontal cortex of rats chronically administered carbamazepine (CBZ) or lamotrigine (LTG) to produce plasma concentrations therapeutically relevant to bipolar disorder. Chronic CBZ and LTG significantly increased BDNF and Bcl-2 mRNA and protein levels in the frontal cortex. A common mechanism of action of mood stabilizers in the treatment of bipolar disorder may involve neuroprotection mediated by upregulation of brain BDNF and Bcl-2 expression.

Keywords

BDNF Bcl-2 Lithium Valproate Carbamazepine Lamotrigine Brain Bipolar Disorder Rat 

Abbreviations

AP-2

Activator protein-2

BDNF

Brain derived neurotrophic factor

Bcl-2

B-cell lymphoma-2

BD

Bipolar disorder

CBZ

Carbamazepine

CREB

cAMP response element binding protein

LTG

Lamotrigine

pCREB

Phosphorylated CREB

Notes

Acknowledgements

This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We thank the National Cancer Institute (NCI), Center for Cancer Research (CCR) Fellows Editorial Board, for proofreading the manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yunyoung C. Chang
    • 1
  • Stanley I. Rapoport
    • 1
  • Jagadeesh S. Rao
    • 1
  1. 1.Brain Physiology and Metabolism Section, National Institute on AgingNational Institutes of HealthBethesdaUSA

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