title: The involvement of retinoic acid receptor-alpha in corticotropin-releasing hormone gene expression and affective disorders.
abstract: BACKGROUND
  Corticotropin-releasing hormone (CRH) is considered the central driving force in the stress response and plays a key role in the pathogenesis of depression. Retinoic acid (RA) has been suggested by clinical studies to be associated with affective disorders.
  
  
  METHODS
  First, hypothalamic tissues of 12 patients with affective disorders and 12 matched control subjects were studied by double-label immunofluorescence to analyze the expression of CRH and retinoic acid receptor-alpha (RAR-alpha). Second, critical genes involved in the RA signaling pathways were analyzed in a rat model of depression. Finally, the regulatory effect of RAR-alpha on CRH gene expression was studied in vitro.
  
  
  RESULTS
  We found that the expression of RAR-alpha was colocalized with CRH neurons in human hypothalamic paraventricular nucleus (PVN). The density of RAR-alpha-immunoreactive neurons and CRH-RAR-alpha double-staining neurons was significantly increased in the PVN of patients with affective disorders. The ratio of the CRH-RAR-alpha double-staining neurons to the CRH-immunoreactive neurons in affective disorder patients was also increased. Recruitment of RAR-alpha by the CRH promoter was observed in the rat hypothalamus. A dysregulated RA metabolism and signaling was also found in the hypothalamus of a rat model for depression. Finally, in vitro studies demonstrated that RAR-alpha mediated an upregulation of CRH gene expression.
  
  
  CONCLUSIONS
  These results suggest that RAR-alpha might contribute to regulating the activity of CRH neurons in vivo, and the vulnerable character of the critical proteins in RA signaling pathways might provide novel targets for therapeutic strategies for depression.
authors: Department of Neurobiology and Biophysics, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Science, University of Science and Technology of China, Anhui, People's Republic of China.
authors: Xiao-Ning
authors: XN
authors: Chen
authors: Qing-Yuan
authors: QY
authors: Meng
authors: Ai-Min
authors: AM
authors: Bao
authors: Dick F
authors: DF
authors: Swaab
authors: Guang-Hui
authors: GH
authors: Wang
authors: Jiang-Ning
authors: JN
authors: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism* / Q000502:physiology; D050697:Retinal Dehydrogenase / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000502:physiology; D014212:Tretinoin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000607071:RARA protein, human; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082927:retinoic acid binding protein I, cellular; D001127:Arginine Vasopressin; D014212:Tretinoin; D003346:Corticotropin-Releasing Hormone; D000080924:Aldehyde Dehydrogenase 1 Family; C523119:Aldh1a1 protein, rat; C523120:Aldh1a3 protein, rat; D050697:Retinal Dehydrogenase