Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

Xin-Rui Qi, Juan Zhao, Ji Liu, Hui Fang, Dick F Swaab, Jiang-Ning Zhou

Research output: Contribution to journal/periodicalArticleScientificpeer-review

491 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalCerebral Cortex
Issue number1
Publication statusPublished - Jan 2015


  • Aged
  • Aldehyde Dehydrogenase
  • Aldehyde Oxidoreductases
  • Animals
  • Bipolar Disorder
  • Brain-Derived Neurotrophic Factor
  • CHO Cells
  • Cell Line, Tumor
  • Cricetulus
  • Depressive Disorder, Major
  • Female
  • Gyrus Cinguli
  • Humans
  • Male
  • Membrane Glycoproteins
  • Neuroblastoma
  • Neurons
  • Prefrontal Cortex
  • Protein-Tyrosine Kinases
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Retinoid X Receptor alpha
  • Retinoid X Receptor beta
  • Retinoid X Receptors
  • Signal Transduction
  • Stress, Psychological


Dive into the research topics of 'Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders'. Together they form a unique fingerprint.

Cite this