title: Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder.
abstract: BACKGROUND
  Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS). The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter.
  
  
  METHODS
  In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM). Levels of Cytochrome c (Cyt-C) was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM). The change of thiamine monophosphatase (TMP) levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM.
  
  
  RESULTS
  Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS.
  
  
  CONCLUSIONS
  The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated with PTSD.
authors.affiliation: Department of Electron Microscopy, Basic Medical Sciences College, China Medical University, 92 North 2nd Road, Shenyang 110001Liaoning, China.
authors.forename: Dongjuan
authors.initials: D
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D045304:Cytochromes c; C022734:thiamine monophosphatase; D010744:Phosphoric Monoester Hydrolases