title: Protective effects of the novel adenosine derivative WS0701 in a mouse model of posttraumatic stress disorder.
abstract: OBJECTIVE
  To investigate the effects of the novel N6-substituted adenosine derivative {(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-[(4-hydroxy-3-methoxybenzyl)amino]-9H-purin-9-yl]tetrahydrofuran-2-yl} methyl decanoate (WS0701) on stress-induced excessive fear, anxiety, and cognitive deficits in a mouse model of posttraumatic stress disorder (PTSD).
  
  
  METHODS
  Male mice underwent a conditioned foot shock and single prolonged stress procedure to induce PTSD. Contextual/cued fear, elevated plus-maze, open field and novel object recognition tests were conduced to assess PTSD-like behaviors. From d 1, the mice were orally administered WS0701 (7.5, 15, or 30 mg·kg(-1)·d(-1)) or paroxetine (10 mg·kg(-1)·d(-1)) for two weeks. Apoptosis of hippocampal neurons was detected using flow cytometry and TUNEL staining, and expression of Bcl-2 and Bax in the hippocampus was measured with Western boltting and qPCR assays.
  
  
  RESULTS
  WS0701 administration significantly alleviated fear, anxious behaviors and memory deficits in the mouse model of PTSD. Furthermore, WS0701 administration significantly reduced the stress-induced apoptosis of hippocampal neurons, and increased the Bcl-2/Bax ratio in the hippocampus. The positive control drug paroxetine exerted similar effects on PTSD-like behaviors and hippocampal neuron apoptosis in the mouse model of PTSD, which were comparable to those caused by the high dose of WS0701.
  
  
  CONCLUSIONS
  WS0701 effectively mitigates stress-induced PTSD-like behaviors in mice, partly via inhibition of neuronal apoptosis in the hippocampus.
authors: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Zhong-lin
authors: ZL
authors: Huang
authors: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Rui
authors: R
authors: Liu
authors: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Xiao-yu
authors: XY
authors: Bai
authors: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Gang
authors: G
authors: Zhao
authors: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Jun-ke
authors: JK
authors: Song
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Song
authors: S
authors: Wu
authors: 1] Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China [2] State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Guan-hua
authors: GH
authors: Du
mesh_terms: D000241:Adenosine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; C561084:O2',O3',O5'-triacetyl-N6-(3-hydroxylaniline)adenosine; C063248:6-(5-hydroxy-2-pyridylmethylamino)-9-beta-ribofuranosylpurine; D000241:Adenosine