title: Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.
abstract: BACKGROUND
  Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive.
  
  
  METHODS
  Male and female rats were exposed to chronic variable mild stress (CVMS) after which immediate early gene products, corticotropin-releasing factor (CRF) mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN), oval (BSTov) and fusiform (BSTfu) parts of the bed nucleus of the stria terminalis, and central amygdala (CeA).
  
  
  RESULTS
  CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females.
  
  
  CONCLUSIONS
  The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.
authors: Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors: Linda
authors: L
authors: Sterrenburg
authors: Balázs
authors: B
authors: Gaszner
authors: Jeroen
authors: J
authors: Boerrigter
authors: Lennart
authors: L
authors: Santbergen
authors: Mattia
authors: M
authors: Bramini
authors: Evan
authors: E
authors: Elliott
authors: Alon
authors: A
authors: Chen
authors: Bernard W M M
authors: BW
authors: Peeters
authors: Eric W
authors: EW
authors: Roubos
authors: Tamás
authors: T
authors: Kozicz
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D002908:Chronic Disease; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008954:Models, Biological; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000378:metabolism / Q000473:pathology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology
chemical_list: D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone