title: Immobilization stress elevates tryptophan hydroxylase mRNA and protein in the rat raphe nuclei.
abstract: BACKGROUND
  Stress triggers adaptive and maladaptive changes in the central nervous system, including activation of the hypothalamic-pituitary-adrenal axis, and can trigger mood disorders and posttraumatic stress disorder. We examined the effect of immobilization stress (IMO) on gene expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, and the role of cortisol in that response.
  
  
  METHODS
  Regular and adrenalectomized Sprague-Dawley rats were exposed to various repetitions of IMO. Tryptophan hydroxylase messenger ribonucleic acid (mRNA) was determined by competitive reverse transcriptase polymerase chain reaction, and TPH protein was examined by immunoblot and immunocytochemistry.
  
  
  RESULTS
  Elevation of TPH mRNA by IMO was tissue-specific and dose-dependent. A single IMO elicited a threefold rise in TPH mRNA in median raphe nucleus (MRN), but repeated (3x) IMOs were needed for similar response in dorsal raphe nucleus (DRN). Repeated daily IMO, up to 7 days, triggered a robust induction (6-10-fold) in TPH mRNA, accompanied by corresponding rise in TPH protein levels in raphe nuclei but not in the pineal gland. The rise in TPH immunoreactivity was widespread throughout the DRN and MRN. Bilateral adrenalectomy did not prevent the IMO-triggered increase in TPH immunoreactive protein in the raphe nuclei.
  
  
  CONCLUSIONS
  This study reveals adrenal glucocorticoid-independent induction of TPH gene expression in raphe nuclei in response to immobilization stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Firas M
authors.initials: FM
authors.lastname: Chamas
authors.forename: Mark D
authors.initials: MD
authors.lastname: Underwood
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.forename: Lidia
authors.initials: L
authors.lastname: Serova
authors.forename: Suham A
authors.initials: SA
authors.lastname: Kassir
authors.forename: John J
authors.initials: JJ
authors.lastname: Mann
authors.forename: Esther L
authors.initials: EL
authors.lastname: Sabban
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007103:Immobilization; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000201:enzymology* / Q000209:etiology; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014365:Tryptophan Hydroxylase