Advertisement

Psychopharmacology

, Volume 232, Issue 16, pp 3081–3090 | Cite as

Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide

  • Mohammad Hadi Gharedaghi
  • Reza Rahimian
  • Ahmad Reza DehpourEmail author
  • Yashar Yousefzadeh-Fard
  • Ahmad Mohammadi-FaraniEmail author
Original Investigation

Abstract

Rationale

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.

Objectives

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.

Conclusion

DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.

Keywords

Dinitrobenzene sulfonic acid-induced colitis Y-maze paradigm Memory N-methyl d-aspartate MK-801 Memantine Nitric oxide Aminoguanidine Passive avoidance test Mice 

Notes

Acknowledgments

This study was supported by a grant from the Vice Chancellor of Research of Kermanshah University of Medical Sciences. The protocol for this study was approved by our institution’s animal use and care committee (Department of Pharmacology, Kermanshah University of Medical Sciences, Kermanshah, Iran), and the experiments were performed in accordance with Iranian laws.

Conflict of interest

The authors declare no conflict of interests.

References

  1. Advokat C, Pellegrin AI (1992) Excitatory amino acids and memory: evidence from research on Alzheimer’s disease and behavioral pharmacology. Neurosci Biobehav Rev 16:13–24PubMedCrossRefGoogle Scholar
  2. Attree EA, Dancey CP, Keeling D, Wilson C (2003) Cognitive function in people with chronic illness: inflammatory bowel disease and irritable bowel syndrome. Appl Neuropsychol 10:96–104PubMedCrossRefGoogle Scholar
  3. Babaei R, Javadi-Paydar M, Sharifian M, Mahdavian S, Almasi-Nasrabadi M, Norouzi A, Dehpour AR (2012) Involvement of nitric oxide in pioglitazone memory improvement in morphine-induced memory impaired mice. Pharmacol Biochem Behav 103:313–321PubMedCrossRefGoogle Scholar
  4. Ben Menachem-Zidon O, Goshen I, Kreisel T, Ben Menahem Y, Reinhartz E, Ben Hur T, Yirmiya R (2008) Intrahippocampal transplantation of transgenic neural precursor cells overexpressing interleukin-1 receptor antagonist blocks chronic isolation-induced impairment in memory and neurogenesis. Neuropsychopharmacology 33:2251–2262PubMedCrossRefGoogle Scholar
  5. Bhargava HN, Thorat SN (1994) Effect of dizocilpine (MK-801) on analgesia and tolerance induced by U-50,488H, a kappa-opioid receptor agonist, in the mouse. Brain Res 649:111–116PubMedCrossRefGoogle Scholar
  6. Cannarile L, Cuzzocrea S, Santucci L, Agostini M, Mazzon E, Esposito E, Muia C, Coppo M, Di Paola R, Riccardi C (2009) Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis. Gastroenterology 136:530–541PubMedCrossRefGoogle Scholar
  7. Chen M, Lee G, Kwong LN, Lamont S, Chaves C (2012) Cerebral white matter lesions in patients with Crohn’s disease. J Neuroimaging 22:38–41PubMedCrossRefGoogle Scholar
  8. Cohn J, Cory-Slechta DA (1994) Lead exposure potentiates the effects of NMDA on repeated learning. Neurotoxicol Teratol 16:455–465PubMedCrossRefGoogle Scholar
  9. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A (2009) Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis 15:852–857PubMedCrossRefGoogle Scholar
  10. D’Argenio G, Valenti M, Scaglione G, Cosenza V, Sorrentini I, Di Marzo V (2006) Up-regulation of anandamide levels as an endogenous mechanism and a pharmacological strategy to limit colon inflammation. FASEB J 20:568–570PubMedGoogle Scholar
  11. de Lau LM, de Vries JM, van der Woude CJ, Kuipers EJ, Siepman DA, Sillevis Smitt PA, Hintzen RQ (2009) Acute CNS white matter lesions in patients with inflammatory bowel disease. Inflamm Bowel Dis 15:576–580PubMedCrossRefGoogle Scholar
  12. Dellu F, Mayo W, Cherkaoui J, Le Moal M, Simon H (1992) A two-trial memory task with automated recording: study in young and aged rats. Brain Res 588:132–139PubMedCrossRefGoogle Scholar
  13. Dhir A, Kulkarni SK (2008) Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test. Indian J Exp Biol 46:164–170PubMedGoogle Scholar
  14. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O (2003) Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 100:13632–13637PubMedCentralPubMedCrossRefGoogle Scholar
  15. Everhart JE, Ruhl CE (2009) Burden of digestive diseases in the United States part II: lower gastrointestinal diseases. Gastroenterology 136:741–754PubMedCrossRefGoogle Scholar
  16. Figueiredo JG, Bitencourt FS, Cunha TM, Luz PB, Nascimento KS, Mota MR, Sampaio AH, Cavada BS, Cunha FQ, Alencar NM (2010) Agglutinin isolated from the red marine alga Hypnea cervicornis J. Agardh reduces inflammatory hypernociception: involvement of nitric oxide. Pharmacol Biochem Behav 96:371–377PubMedCrossRefGoogle Scholar
  17. Garate I, Garcia-Bueno B, Madrigal JL, Caso JR, Alou L, Gomez-Lus ML, Mico JA, Leza JC (2013) Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway. Biol Psychiatry 73:32–43PubMedCrossRefGoogle Scholar
  18. Gibertini M, Newton C, Friedman H, Klein TW (1995) Spatial learning impairment in mice infected with Legionella pneumophila or administered exogenous interleukin-1-beta. Brain Behav Immun 9:113–128PubMedCrossRefGoogle Scholar
  19. Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12(Suppl 1):S3–S9PubMedCrossRefGoogle Scholar
  20. Harrison NA, Doeller CF, Voon V, Burgess N, Critchley HD (2014) Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism. Biol Psychiatry 76:585–593PubMedCentralPubMedCrossRefGoogle Scholar
  21. Hendrickson BA, Gokhale R, Cho JH (2002) Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 15:79–94PubMedCentralPubMedCrossRefGoogle Scholar
  22. Hu S, Sheng WS, Ehrlich LC, Peterson PK, Chao CC (2000) Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation 7:153–159PubMedCrossRefGoogle Scholar
  23. Hyphantis TN, Tomenson B, Bai M, Tsianos E, Mavreas V, Creed F (2010) Psychological distress, somatization, and defense mechanisms associated with quality of life in inflammatory bowel disease patients. Dig Dis Sci 55:724–732PubMedCrossRefGoogle Scholar
  24. Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304:1787–1794PubMedCentralPubMedCrossRefGoogle Scholar
  25. Kamikawa H, Hori T, Nakane H, Aou S, Tashiro N (1998) IL-1beta increases norepinephrine level in rat frontal cortex: involvement of prostanoids, NO, and glutamate. Am J Physiol 275:R803–R810PubMedGoogle Scholar
  26. Katsanos K, Papakostas V, Konitsiotis S, Mpaltayiannis G, Tsianos E (2003) Amnesia and brain atrophy with focal white matter lesion in a 30-year old male with Crohn’s disease. Ann Gastroenterol 16:173–176Google Scholar
  27. Katsuki H, Nakai S, Hirai Y, Akaji K, Kiso Y, Satoh M (1990) Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur J Pharmacol 181:323–326PubMedCrossRefGoogle Scholar
  28. Kelly PH, Bondolfi L, Hunziker D, Schlecht HP, Carver K, Maguire E, Abramowski D, Wiederhold KH, Sturchler-Pierrat C, Jucker M, Bergmann R, Staufenbiel M, Sommer B (2003) Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging 24:365–378PubMedCrossRefGoogle Scholar
  29. Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, Collins SM (2002) Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 70:5931–5937PubMedCentralPubMedCrossRefGoogle Scholar
  30. Kim JJ, Bridle BW, Ghia JE, Wang H, Syed SN, Manocha MM, Rengasamy P, Shajib MS, Wan Y, Hedlund PB, Khan WI (2013) Targeted inhibition of serotonin type 7 (5-HT7) receptor function modulates immune responses and reduces the severity of intestinal inflammation. J Immunol (Baltimore, Md: 1950) 190:4795–4804CrossRefGoogle Scholar
  31. Kovacs AD, Saje A, Wong A, Ramji S, Cooper JD, Pearce DA (2012) Age-dependent therapeutic effect of memantine in a mouse model of juvenile Batten disease. Neuropharmacology 63:769–775PubMedCentralPubMedCrossRefGoogle Scholar
  32. Laflamme N, Rivest S (2001) Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15:155–163PubMedCrossRefGoogle Scholar
  33. Levine JS, Burakoff R (2011) Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y) 7:235–241Google Scholar
  34. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMedGoogle Scholar
  35. Lucas SM, Rothwell NJ, Gibson RM (2006) The role of inflammation in CNS injury and disease. Br J Pharmacol 147(Suppl 1):S232–S240PubMedCentralPubMedGoogle Scholar
  36. Madrigal JL, Moro MA, Lizasoain I, Lorenzo P, Castrillo A, Bosca L, Leza JC (2001) Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor kappaB-mediated mechanisms. J Neurochem 76:532–538PubMedCrossRefGoogle Scholar
  37. Madrigal JL, Hurtado O, Moro MA, Lizasoain I, Lorenzo P, Castrillo A, Bosca L, Leza JC (2002) The increase in TNF-alpha levels is implicated in NF-kappaB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Neuropsychopharmacology 26:155–163PubMedCrossRefGoogle Scholar
  38. Maier SF, Watkins LR (1995) Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res 695:279–282PubMedCrossRefGoogle Scholar
  39. Moghaddam B (1993) Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. J Neurochem 60:1650–1657PubMedCrossRefGoogle Scholar
  40. Morris RG, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319:774–776PubMedCrossRefGoogle Scholar
  41. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803PubMedGoogle Scholar
  42. Munhoz CD, Garcia-Bueno B, Madrigal JL, Lepsch LB, Scavone C, Leza JC (2008) Stress-induced neuroinflammation: mechanisms and new pharmacological targets. Braz J Med Biol Res 41:1037–1046PubMedCrossRefGoogle Scholar
  43. Natah SS, Mouihate A, Pittman QJ, Sharkey KA (2005) Disruption of the blood–brain barrier during TNBS colitis. Neurogastroenterol Motil 17:433–446PubMedCrossRefGoogle Scholar
  44. Onogi H, Ishigaki S, Nakagawasai O, Arai-Kato Y, Arai Y, Watanabe H, Miyamoto A, Tan-no K, Tadano T (2009) Influence of memantine on brain monoaminergic neurotransmission parameters in mice: neurochemical and behavioral study. Biol Pharm Bull 32:850–855PubMedCrossRefGoogle Scholar
  45. Parsons CG, Stoffler A, Danysz W (2007) Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system—too little activation is bad, too much is even worse. Neuropharmacology 53:699–723PubMedCrossRefGoogle Scholar
  46. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmacher T (2001) Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 58:445–452PubMedCrossRefGoogle Scholar
  47. Riazi K, Honar H, Homayoun H, Demehri S, Bahadori M, Dehpour AR (2004) Intestinal inflammation alters the susceptibility to pentylenetetrazole-induced seizure in mice. J Gastroenterol Hepatol 19:270–277PubMedCrossRefGoogle Scholar
  48. Riazi K, Galic MA, Kuzmiski JB, Ho W, Sharkey KA, Pittman QJ (2008) Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci U S A 105:17151–17156PubMedCentralPubMedCrossRefGoogle Scholar
  49. Riazi K, Galic MA, Pittman QJ (2010) Contributions of peripheral inflammation to seizure susceptibility: cytokines and brain excitability. Epilepsy Res 89:34–42PubMedCrossRefGoogle Scholar
  50. Ribeiro DE, Maiolini VM, Soncini R, Antunes-Rodrigues J, Elias LL, Vilela FC, Giusti-Paiva A (2013) Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice. Pharmacol Biochem Behav 103:535–540PubMedCrossRefGoogle Scholar
  51. Scheid R, Teich N (2007) Neurologic manifestations of ulcerative colitis. Eur J Neurol 14:483–493PubMedCrossRefGoogle Scholar
  52. Schmidt S, Mellstrom D, Norjavaara E, Sundh V, Saalman R (2012) Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 55:511–518PubMedCrossRefGoogle Scholar
  53. Schneider H, Pitossi F, Balschun D, Wagner A, del Rey A, Besedovsky HO (1998) A neuromodulatory role of interleukin-1beta in the hippocampus. Proc Natl Acad Sci U S A 95:7778–7783PubMedCentralPubMedCrossRefGoogle Scholar
  54. Shajib MS, Wang H, Kim JJ, Sunjic I, Ghia JE, Denou E, Collins M, Denburg JA, Khan WI (2013) Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation. PLoS One 8, e72774PubMedCentralPubMedCrossRefGoogle Scholar
  55. Sturiale S, Barbara G, Qiu B, Figini M, Geppetti P, Gerard N, Gerard C, Grady EF, Bunnett NW, Collins SM (1999) Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P. Proc Natl Acad Sci U S A 96:11653–11658PubMedCentralPubMedCrossRefGoogle Scholar
  56. Takahashi K, Funata N, Ikuta F, Sato S (2008) Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2. J Neuroinflammation 5:11PubMedCentralPubMedCrossRefGoogle Scholar
  57. Thorat SN, Bhargava HN (1994) Effects of NMDA receptor blockade and nitric oxide synthase inhibition on the acute and chronic actions of delta 9-tetrahydrocannabinol in mice. Brain Res 667:77–82PubMedCrossRefGoogle Scholar
  58. van Dam AM, Poole S, Schultzberg M, Zavala F, Tilders FJ (1998) Effects of peripheral administration of LPS on the expression of immunoreactive interleukin-1 alpha, beta, and receptor antagonist in rat brain. Ann N Y Acad Sci 840:128–138PubMedCrossRefGoogle Scholar
  59. Van Dam D, D’Hooge R, Staufenbiel M, Van Ginneken C, Van Meir F, De Deyn PP (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 17:388–396PubMedCrossRefGoogle Scholar
  60. Villaran RF, Espinosa-Oliva AM, Sarmiento M, De Pablos RM, Arguelles S, Delgado-Cortes MJ, Sobrino V, Van Rooijen N, Venero JL, Herrera AJ, Cano J, Machado A (2010) Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson’s disease. J Neurochem 114:1687–1700PubMedCrossRefGoogle Scholar
  61. Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, Binaglia M, Corsini E, Di Luca M, Galli CL, Marinovich M (2003) Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 23:8692–8700PubMedGoogle Scholar
  62. Wang GW, Cai JX (2008) Reversible disconnection of the hippocampal-prelimbic cortical circuit impairs spatial learning but not passive avoidance learning in rats. Neurobiol Learn Mem 90:365–373PubMedCrossRefGoogle Scholar
  63. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5:88PubMedCentralPubMedCrossRefGoogle Scholar
  64. Wong TP, Howland JG, Robillard JM, Ge Y, Yu W, Titterness AK, Brebner K, Liu L, Weinberg J, Christie BR, Phillips AG, Wang YT (2007) Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment. Proc Natl Acad Sci U S A 104:11471–11476PubMedCentralPubMedCrossRefGoogle Scholar
  65. Yirmiya R, Goshen I (2011) Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25:181–213PubMedCrossRefGoogle Scholar
  66. Zajaczkowski W, Frankiewicz T, Parsons CG, Danysz W (1997) Uncompetitive NMDA receptor antagonists attenuate NMDA-induced impairment of passive avoidance learning and LTP. Neuropharmacology 36:961–971PubMedCrossRefGoogle Scholar
  67. Zoladz PR, Campbell AM, Park CR, Schaefer D, Danysz W, Diamond DM (2006) Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane. Pharmacol Biochem Behav 85:298–306PubMedCrossRefGoogle Scholar
  68. Zou JY, Crews FT (2005) TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 1034:11–24PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Mohammad Hadi Gharedaghi
    • 1
    • 2
  • Reza Rahimian
    • 1
  • Ahmad Reza Dehpour
    • 1
    • 3
    Email author
  • Yashar Yousefzadeh-Fard
    • 1
    • 4
  • Ahmad Mohammadi-Farani
    • 5
    • 6
    Email author
  1. 1.Department of Pharmacology, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of SurgeryMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Experimental Medicine Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Division of Molecular Imaging and Neuropathology, Department of PsychiatryNew York State Psychiatry Institute, Columbia University Medical CenterNew YorkUSA
  5. 5.Novel Drug Delivery Research CenterKermanshah University of Medical SciencesKermanshahIran
  6. 6.Department of Pharmacology, Toxicology and Medical Services, Faculty of PharmacyKermanshah University of Medical SciencesKermanshahIran

Personalised recommendations