Abstract
Aims Rutin is one of the flavonoids that has many beneficial effects on the health. Previously, we showed that rutin has a protective effect on trimethyltin (TMT)-induced memory dysfunction in rats. The aim of this study was to investigate the protective effects of rutin on TMT-induced hippocampal injury and the time course profiles of these effects in rats. Methods Four-week-old male Sprague-Dawley (SD) rats were fed chow with or without rutin (0.75%) during the experimental period and were administered with a single dose of TMT (8.5 mg/kg b.w., p.o.) or vehicle at 6 weeks of age. The rats were sacrificed 5, 10, or 20 days after the TMT administration and then histological and molecular examinations of the hippocampus were performed. Results Rutin supplementation suppressed the TMT-induced decrease in the number of hippocampal pyramidal neurons 20 days after TMT administration. The TMT-induced up-regulation of the mRNA expression levels of reactive microglia marker and pro-inflammatory cytokines were reversed by rutin supplementation 10 or 20 days after the TMT administration. Conclusions These results suggested that the neuroprotective effect of rutin on TMT-induced spatial memory impairment could be attributable to its inhibitory effect against microglial activation and its role in synapse formation via neurotrophic factors in the hippocampus.
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Abbreviations
- TMT:
-
Trimethyltin
- SD:
-
Sprague-Dawley
- CA:
-
Cornu ammonis
- GFAP:
-
Glial fibrillary acidic protein
- IL:
-
Interleukin
- TNF:
-
Tumor necrosis factor
- BDNF:
-
Brain-derived neurotrophic factor
- bFGF:
-
Basic fibroblast growth factor
- PCR:
-
polymerase chain reaction
- Ct:
-
Cycle of threshold
- RT:
-
Reverse transcription
- ANOVA:
-
Analysis of variance
- PLSD:
-
Protected least-squares difference
- CNS:
-
Central nervous system
References
Andersson H, Wetmore C, Lindqvist E, Luthman J, Olson L (1997) Trimethyltin exposure in the rat induces delayed changes in brain-derived neurotrophic factor, fos, and heat shock protein 70. Neurotoxicology 18:147–159
Bekinschtein P, Cammarota M, Izquierdo I, Medina JH (2008) BDNF and memory formation and storage. Neuroscientist 14:147–156. doi:10.1177/1073858407305850
Benveniste EN (1997) Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 75:165–173. doi:10.1007/s001090050101
Brown AW, Aldridge WN, Street BW, Verschoyle RD (1979) The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat. Am J Pathol 97:59–82
Chang LW, Dyer RS (1983) A time-course study of trimethyltin induced neuropathology in rats. Neurobehav Toxicol Teratol 5:443–459
Chang LW, Dyer RS (1985) Septotemporal gradients of trimethyltin-induced hippocampal lesions. Neurobehav Toxicol Teratol 7:43–49
Cruz T, Galvez J, Ocete MA, Crespo ME, Sanchez de Medina LHF, Zarzuelo A (1998) Oral administration of rutoside can ameliorate inflammatory bowel disease in rats. Life Sci 62:687–695. doi:10.1016/S0024-3205(97)01164-8
Goutan E, Marti E, Ferrer I (1998) BDNF, and full length and truncated TrkB expression in the hippocampus of the rat following kainic acid excitotoxic damage. Evidence of complex time-dependent and cell-specific responses. Brain Res Mol Brain Res 59:154–164. doi:10.1016/S0169-328X(98)00156-9
Guardia T, Rotelli AE, Juarez AO, Pelzer LE (2001) Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 56:683–687. doi:10.1016/S0014-827X(01)01111-9
Gupta R, Singh M, Sharma A (2003) Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury. Pharmacol Res 48:209–215. doi:10.1016/S1043-6618(03)00102-6
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394. doi:10.1038/nn1997
Holasova M, Fiedlerova V, Smrcinova H, Orsak M, Lachman J, Vavreinova S (2002) Buckwheat-the source of antioxidant activity in functional foods. Food Res Int 35:207–211. doi:10.1016/S0963-9969(01)00185-5
Hunsaker MR, Lee B, Kesner RP (2008) Evaluating the temporal context of episodic memory: the role of CA3 and CA1. Behav Brain Res 188:310–315. doi:10.1016/j.bbr.2007.11.015
Imai H, Nishimura T, Sadamatsu M, Liu Y, Kabuto M, Kato N (2001) Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus. Exp Neurol 171:22–28. doi:10.1006/exnr.2001.7725
Ishida N, Akaike M, Tsutsumi S, Kanai H, Masui A, Sadamatsu M, Kuroda Y, Watanabe Y, McEwen BS, Kato N (1997) Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment. Neuroscience 81:1183–1191. doi:10.1016/S0306-4522(97)00220-0
Joseph JA, Shukitt-Hale B, Casadesus G (2005) Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr 81:313S–316S
Kamalakkannan N, Prince PS (2006) Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 98:97–103. doi:10.1111/j.1742-7843.2006.pto_241.x
Kim H, Kong H, Choi B, Yang Y, Kim Y, Lim MJ, Neckers L, Jung Y (2005) Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease. Pharm Res 22:1499–1509. doi:10.1007/s11095-005-6250-z
Koda T, Kuroda Y, Imai H (2008) Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats. Nutr Res 28:629–634. doi:10.1016/j.nutres.2008.06.004
Kutscher CL (1992) A morphometric analysis of trimethyltin-induced change in rat brain using the Timm technique. Brain Res Bull 28:519–527. doi:10.1016/0361-9230(92)90098-I
Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165:1364–1371. doi:10.1093/aje/kwm036
Liu Y, Imai H, Sadamatsu M, Tsunashima K, Kato N (2005) Cytokines participate in neuronal death induced by trimethyltin in the rat hippocampus via type II glucocorticoid receptors. Neurosci Res 51:319–327. doi:10.1016/j.neures.2004.12.005
Maier WE, Brown HW, Tilson HA, Luster MI, Harry GJ (1995) Trimethyltin increases interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha mRNA levels in rat hippocampus. J Neuroimmunol 59:65–75. doi:10.1016/0165-5728(95)00026-X
Meydani M (2001) Nutrition interventions in aging and age-associated disease. Ann N Y Acad Sci 928:226–235
Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683. doi:10.1038/297681a0
Mukoda T, Sun B, Ishiguro A (2001) Antioxidant activities of buckwheat hull extract toward various oxidative stress in vitro and in vivo. Biol Pharm Bull 24:209–213. doi:10.1248/bpb.24.209
Nakazawa K, McHugh TJ, Wilson MA, Tonegawa S (2004) NMDA receptors, place cells and hippocampal spatial memory. Nat Rev Neurosci 5:361–372. doi:10.1038/nrn1385
Nishimura T, Imai H, Minabe Y, Sawa A, Kato N (2006) Beneficial effects of FK506 for experimental temporal lobe epilepsy. Neurosci Res 56:386–390. doi:10.1016/j.neures.2006.08.006
Pu F, Mishima K, Irie K, Motohashi K, Tanaka Y, Orito K, Egawa T, Kitamura Y, Egashira N, Iwasaki K, Fujiwara M (2007) Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats. J Pharmacol Sci 104:329–334. doi:10.1254/jphs.FP0070247
Stubley-Weatherly L, Harding JW, Wright JW (1996) Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats. Brain Res 716:29–38. doi:10.1016/0006-8993(95)01589-2
Takano T, Oberheim NA, Cotrinam ML, Nedergaard M (2008) Astrocytes and ischemic injury. Stroke. doi:10.1161/strokeaha.108.533166
Tsutsumi S, Akaike M, Arimitsu H, Imai H, Kato N (2002) Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats. Exp Neurol 173:86–94. doi:10.1006/exnr.2001.7824
van Praag H, Lucero MJ, Yeo GW, Stecker K, Heivand N, Zhao C, Yip E, Afanador M, Schroeter H, Hammerstone J, Gage FH (2007) Plant-derived flavanol(-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27:5869–5878. doi:10.1523/JNEUROSCI.0914-07.2007
Vicario-Abejon C, Owens D, McKay R, Segal M (2002) Role of neurotrophins in central synapse formation and stabilization. Nat Rev Neurosci 3:965–974. doi:10.1038/nrn988
Zielinski H, Michalska A, Piskula MK, Kozlowska H (2006) Antioxidants in thermally treated buckwheat groats. Mol Nutr Food Res 50:824–832. doi:10.1002/mnfr.200500258
Acknowledgment
The authors thank Hirohisa Takano (National Institute for Environmental Studies, Japan) for helpful comment on the design of this study.
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Koda, T., Kuroda, Y. & Imai, H. Rutin Supplementation in the Diet has Protective Effects Against Toxicant-Induced Hippocampal Injury by Suppression of Microglial Activation and Pro-Inflammatory Cytokines. Cell Mol Neurobiol 29, 523–531 (2009). https://doi.org/10.1007/s10571-008-9344-4
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DOI: https://doi.org/10.1007/s10571-008-9344-4