Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression levels in rat frontal cortex.
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.
Chang
Yunyoung C
YC
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S -126, Bethesda, MD 20892, USA.
Rapoport
Stanley I
SI
Rao
Jagadeesh S
JS
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002220:Carbamazepine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D000077213:Lamotrigine; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014227:Triazines / Q000494:pharmacology*; D015854:Up-Regulation
D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine