title: Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl-2/Bax pathway.
abstract: OBJECTIVE
  The aim of this study was to identify whether arsenic (As) exposure could induce hippocampal neural apoptosis in vivo.
  
  
  METHODS
  Sixty-four mice were randomly divided into 4 groups of 16 each. Group 1 orally received drinking water alone as a control. Groups 2-4 were given arsenic trioxide (As2O3) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. All the treatments continued for 60 days. Morphological changes in the hippocampus were observed by HE staining. Apoptosis in the hippocampus was examined by TUNEL assay and transmission electron microscopy. The expression levels of Bcl-2 and Bax genes and their proteins in the hippocampus were determined by real-time PCR and Western blotting. The activity of caspase-3 was determined by spectrophotometry.
  
  
  RESULTS
  Abnormal histopathological changes and apoptosis were found in the hippocampus of As-exposed mice. The expressions of the Bcl-2 gene and its protein in the hippocampus of As-exposed mice were significantly lower than those in the control group (p<0.05). However, the expressions of the Bax gene and its protein, and the expression ratio of Bax/Bcl-2 in the hippocampus were significantly higher in the groups exposed to As than in the control group (p<0.05). Moreover, the activity of caspase-3 in the hippocampus of mice exposed to As was higher than that in the control (p<0.05).
  
  
  CONCLUSIONS
  These results indicate that subchronic exposure to As induces apoptosis in the hippocampus of mice by disturbing normal Bax/Bcl-2 regulatory pathways. Meanwhile, it is suggested that the induced apoptosis in the hippocampus may be at least partly responsible for As-induced neurotoxicity.
authors: Department of Occupational and Environmental Health, Dalian Medical University.
authors: Yachen
authors: Y
authors: Wang
authors: Canming
authors: C
authors: Bai
authors: Huai
authors: H
authors: Guan
authors: Ruolin
authors: R
authors: Chen
authors: Xiaoxu
authors: X
authors: Wang
authors: Bingwen
authors: B
authors: Wang
authors: Hetian
authors: H
authors: Jin
authors: Fengyuan
authors: F
authors: Piao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects*; D013053:Spectrophotometry; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; D001151:Arsenic