title: Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide.
abstract: BACKGROUND
  Many peripheral diseases are associated with a decline in cognitive function. In this regard, there have been reports of patients with inflammatory bowel disease and an otherwise unexplained memory impairment.
  
  
  OBJECTIVE
  We sought to assess the memory performance of mice with colitis. We also investigated the roles of N-methyl D-aspartate (NMDA) receptors and nitric oxide (NO) as possible mediators of colitis-induced amnesia.
  
  
  METHODS
  To induce colitis, male NMRI mice were intrarectally injected with a solution containing dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 μl) under anesthesia. Three days after intrarectal DNBS instillation, spatial recognition and associative memories were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS) inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y-maze task.
  
  
  RESULTS
  Induction of colitis by DNBS impaired spatial recognition memory in the Y-maze task but had no effect on step through latencies in the passive avoidance test. Colitis-induced amnesia was reversed by administering specific doses of MK-801 and memantine (30 μg/kg and 1 mg/kg, respectively) suggesting dysregulated NMDA receptor activation as an underlying mechanism. No effect was seen with lower and higher doses of these drugs, resulting in a bell-shaped dose response curve. Colitis-induced amnesia was also inhibited by aminoguanidine (50 mg/kg), implicating a role for iNOS activation and neuroinflammation in this phenomenon.
  
  
  CONCLUSIONS
  DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
authors.forename: Mohammad Hadi
authors.initials: MH
authors.lastname: Gharedaghi
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.forename: Yashar
authors.initials: Y
authors.lastname: Yousefzadeh-Fard
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mohammadi-Farani
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001557:Benzenesulfonates; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D001557:Benzenesulfonates; D006146:Guanidines; D016194:Receptors, N-Methyl-D-Aspartate; C007488:dinitrobenzenesulfonic acid; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D008559:Memantine