title: Nonsteroidal anti-inflammatory treatment prevents delayed effects of early life stress in rats.
abstract: BACKGROUND
  Early developmental insults can cause dysfunction within parvalbumin (PVB)-containing interneurons in the prefrontal cortex. The neuropsychiatric disorders associated with such dysfunction might involve neuroinflammatory processes. Cyclooxygenase-2 (COX-2) is a key mediator of inflammation and is therefore a potential target for preventive treatment. Here, we investigated whether the developmental trajectories of PVB expression and COX-2 induction in the prelimbic region of the prefrontal cortex are altered after maternal separation stress in male rats.
  
  
  METHODS
  Male rat pups were separated from their mother and littermates for 4 hours/day between postnatal Days 2 and 20. Western blotting and immunohistochemistry were used to analyze PVB and COX-2 expression in the prefrontal cortex and hippocampus. A separate cohort of animals was treated with a COX-2 inhibitor during preadolescence and analyzed for PVB, COX-2, and working memory performance.
  
  
  RESULTS
  We demonstrate that maternal separation causes a reduction of PVB and an increase in COX-2 expression in the prefrontal cortex in adolescence, with concurrent working memory deficits. Parvalbumin was not affected earlier in development. Prophylactic COX-2 inhibition preadolescence prevents PVB loss and improves working memory deficits induced by maternal separation.
  
  
  CONCLUSIONS
  These data are the first to show a preventive pharmacological intervention for the delayed effects of early life stress on prefrontal cortex interneurons and working memory. Our results suggest a possible mechanism for the relationship between early life stress and interneuron dysfunction in adolescence.
authors.affiliation: Laboratory for Developmental Neuropharmacology, McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA. hbrenhouse@mclean.harvard.edu
authors.forename: Heather C
authors.initials: HC
authors.lastname: Brenhouse
authors.forename: Susan L
authors.initials: SL
authors.lastname: Andersen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D008569:Memory Disorders / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D010320:Parvalbumins / Q000096:biosynthesis*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D010320:Parvalbumins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2