Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders.
The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly reduced in the postmortem dorsolateral prefrontal cortex/anterior cingulate cortex (ACC) from elderly depressed patients who did not die from suicide. Decreased mRNA levels of BDNF and TrkB isoforms were also found. Similar alterations were observed in rats subjected to chronic unpredictable mild stress. Along with neurons immunopositive for both retinoic acid receptor-α (RARα) and TrkB, a positive correlation between mRNA levels of the 2 receptors was found in the ACC of control subjects but not of depressed patients. In vitro studies showed that RARα was able to bind to and transactivate the TrkB promoter via a putative RA response element within the TrkB promoter. In conclusion, the retinoid and BDNF-TrkB signaling in the prefrontal cortex are compromised in mood disorders, and the transcriptional upregulation of TrkB by RARα provide a possible mechanism for their interaction. The retinoid signaling pathway that may activate TrkB expression will be an alternative novel target for BDNF-based antidepressant treatment.
['Qi|Xin-Rui|XR|', 'Zhao|Jun|J|', 'Liu|Ji|J|', 'Fang|Hui|H|', 'Swaab|Dick F|DF|', 'Zhou|Jiang-Ning|JN|']
D000368:Aged D000444:Aldehyde Dehydrogenase D000080924:Aldehyde Dehydrogenase 1 Family D000445:Aldehyde Oxidoreductases D000818:Animals D001714:Bipolar Disorder D019208:Brain-Derived Neurotrophic Factor D016466:CHO Cells D045744:Cell Line, Tumor D003412:Cricetulus D003865:Depressive Disorder, Major D005260:Female D006179:Gyrus Cinguli D006801:Humans D008297:Male D008562:Membrane Glycoproteins D009447:Neuroblastoma D009474:Neurons D017397:Prefrontal Cortex D011505:Protein-Tyrosine Kinases D012333:RNA, Messenger D051381:Rats D017207:Rats, Sprague-Dawley D020813:Receptor, trkB D050697:Retinal Dehydrogenase D047490:Retinoid X Receptor alpha D049230:Retinoid X Receptor beta D047488:Retinoid X Receptors D015398:Signal Transduction D013315:Stress, Psychological
mood disorder brain-derived neurotrophic factor dorsolateral prefrontal cortex anterior cingulate cortex retinoic acid receptor-α