title: Physostigmine reverses cognitive dysfunction caused by moderate hypoxia in adult mice.
abstract: BACKGROUND
  Cognitive changes associated with moderate hypoxia in rodents may result from the diminished functioning of central cholinergic neurotransmission. We designed this study to examine whether treatment with physostigmine (PHY), an acetylcholinesterase inhibitor, could improve the impairment of working memory after hypoxic hypoxia.
  
  
  METHODS
  We randomized 90 Swiss Webster, 30-35 g mice (6-8 wks) to three hypoxia groups at fraction of inspired oxygen, FiO2 = 0.10 (1. no treatment; 2. PHY 0.1 mg/kg intraperitoneally administered immediately before; or 3. after hypoxia), or to two room air groups (given either no treatment or PHY after an insult). An object recognition test was used to assess short-term memory function. The object recognition test exploits the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the 15 min training trial, two identical objects were placed in two defined sites of the box. During the test trial performed 1 h later, one of the objects was replaced by a new object with a different shape. The time spent exploring the two objects was automatically recorded by a video camera and associated software. The performance was analyzed with ANOVA, followed by post hoc comparisons using the Newman-Keuls test when appropriate. P values <0.05 were considered significant.
  
  
  RESULTS
  Untreated mice subjected to hypoxia at Fio2 = 0.1 spent significantly less time exploring a novel object on testing day 1 than did untreated mice breathing room air. Performance of the mice subjected to hypoxia, who received physostigmine after, but not before, the insult did not differ from the control group.
  
  
  CONCLUSIONS
  Moderate hypoxia impairs rodents' performance in a working memory task. It appears that changes are transient, because the cognitive functioning of the mice returned to the baseline level 7 days after treatment. Postinsult administration of PHY prevented deterioration of cognitive function. An increased level of acetylcholine in the central nervous system may be responsible for the improved performance of the hypoxia-treated mice.
authors: Department of Anesthesiology, New York University Medical Center, New York, NY 10016, USA. alex.bekker@med.nyu.edu
authors: Alex
authors: A
authors: Bekker
authors: Michael
authors: M
authors: Haile
authors: Kevin
authors: K
authors: Gingrich
authors: Leslie
authors: L
authors: Wenning
authors: Alex
authors: A
authors: Gorny
authors: David
authors: D
authors: Quartermain
authors: Thomas
authors: T
authors: Blanck
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010830:Physostigmine / Q000494:pharmacology* / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D010830:Physostigmine; D000110:Acetylcholinesterase; D000109:Acetylcholine