Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide
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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.
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.
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.
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.
DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.
KeywordsDinitrobenzene sulfonic acid-induced colitis Y-maze paradigm Memory N-methyl d-aspartate MK-801 Memantine Nitric oxide Aminoguanidine Passive avoidance test Mice
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.
- 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
- 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
- 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
- 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
- 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
- Levine JS, Burakoff R (2011) Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y) 7:235–241Google Scholar
- 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
- 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
- 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
- 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