title: Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders.
abstract: 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.
authors: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105BA, The Netherlands.
authors: Xin-Rui
authors: XR
authors: Qi
authors: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
authors: Jun
authors: J
authors: Zhao
authors: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
authors: Ji
authors: J
authors: Liu
authors: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
authors: Hui
authors: H
authors: Fang
authors: Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105BA, The Netherlands.
authors: Dick F
authors: DF
authors: Swaab
authors: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
authors: Jiang-Ning
authors: JN
authors: Zhou
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB; D050697:Retinal Dehydrogenase; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D049230:Retinoid X Receptor beta / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D047488:Retinoid X Receptors; C579455:BDNF protein, human; D000445:Aldehyde Oxidoreductases; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: anterior cingulate cortex; brain-derived neurotrophic factor; dorsolateral prefrontal cortex; mood disorder; retinoic acid receptor-α