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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Research article

Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus

Authors: Woosuk Kim, Dae Young Yoo, Hyo Young Jung, Jong Whi Kim, Kyu Ri Hahn, Hyun Jung Kwon, Miyoung Yoo, Sanghee Lee, Sung Min Nam, Yeo Sung Yoon, Dae Won Kim, In Koo Hwang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

The brain is susceptible to methylmercury toxicity, which causes irreversible damage to neurons and glia and the leaf extract Dendropanax morbifera Léveille (DML) has various biological functions in the nervous system. In this study, we examined the effects of DML on mercury-induced proliferating cells and differentiated neuroblasts.

Methods

Dimethylmercury (5 μg/kg) and galantamine (5 mg/kg) was administered intraperitoneally and/or DML (100 mg/kg) was orally to 7-week-old rats every day for 36 days. One hour after the treatment, novel object recognition test was examined. In addition, spatial probe tests were conducted on the 6th day after 5 days of continuous training in the Morris swim maze. Thereafter, the rats were euthanized for immunohistochemical staining analysis with Ki67 and doublecortin and measurement for acetylcholinesterase (AChE) activity.

Results

Dimethylmercury-treated rats showed reduced discrimination index in novel object recognition test and took longer to find the platform than did control group. Compared with dimethylmercury treatment alone, supplementation with DML or galatamine significantly ameliorated the reduction of discrimination index and reduced the time spent to find the platform. In addition, the number of platform crossings was lower in the dimethylmercury-treated group than in controls, while the administration of DML or galantamine significantly increased the number of crossings than did dimethylmercury treatment alone. Proliferating cells and differentiated neuroblasts, assessed by Ki67 and doublecortin immunohistochemical staining was significantly decreased in the dimethylmercury treated group versus controls. Supplementation with DML or galantamine significantly increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus. In addition, treatment with dimethylmercury significantly increased AChE activity in hippocampal homogenates, while treatment with dimethylmercury+DML or dimethylmercury+galantamine significantly ameliorated this increase.

Conclusions

These results suggest that DML may be a functional food that improves dimethylmercury-induced memory impairment and ameliorates dimethylmercury-induced reduction in proliferating cells and differentiated neuroblasts, and demonstrates corresponding activation of AChE activity in the dentate gyrus.
Literature
1.
Risher JF, Amler SN. Mercury exposure: evaluation and intervention the inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning. Neurotoxicology. 2005;26:691–9.CrossRefPubMed
2.
Yoshida M, Shimada E, Arai F, Yamamura Y. The relation between mercury levels in brain and blood or cerebrospinal fluid (CSF) after mercury exposure. J Toxicol Sci. 1980;5:243–50.CrossRefPubMed
3.
Harada M. Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol. 1995;25:1–24.CrossRefPubMed
4.
Fujimura M, Usuki F. Site-specific neural hyperactivity via the activation of MAPK and PKA/CREB pathways triggers neuronal degeneration in methylmercury-intoxicated mice. Toxicol Lett. 2017;271:66–73.CrossRefPubMed
5.
Edoff K, Raciti M, Moors M, Sundström E, Ceccatelli S. Gestational age and sex influence the susceptibility of human neural progenitor cells to low levels of MeHg. Neurotox Res. 2017;32:683–93.CrossRefPubMedPubMedCentral
6.
Falluel-Morel A, Sokolowski K, Sisti HM, Zhou X, Shors TJ, Dicicco-Bloom E. Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty. J Neurochem. 2007;103:1968–81.CrossRefPubMedPubMedCentral
7.
Karpova NN, Lindholm JS, Kulesskaya N, Onishchenko N, Vahter M, Popova D, Ceccatelli S, Castrén E. TrkB overexpression in mice buffers against memory deficits and depression-like behavior but not all anxiety- and stress-related symptoms induced by developmental exposure to methylmercury. Front Behav Neurosci. 2014;8:315.CrossRefPubMedPubMedCentral
8.
Lu Z, Wu J, Cheng G, Tian J, Lu Z, Bi Y. Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy. Neural Regen Res. 2014;9:1616–20.CrossRefPubMedPubMedCentral
9.
Gutiérrez J, Baraibar AM, Albiñana E, Velasco P, Solís JM, Hernández-Guijo JM. Methylmercury reduces synaptic transmission and neuronal excitability in rat hippocampal slices. Pflugers Arch. 2018;470:1221–30.CrossRefPubMed
10.
Altman J. Postnatal development of the cerebellar cortex in the rat. IV. Spatial organization of bipolar cells, parallel fibers and glial palisades. J Comp Neurol. 1975;163:427–47.CrossRefPubMed
11.
Soriano E, Del Río JA, Martínez A, Supèr H. Organization of the embryonic and early postnatal murine hippocampus. I. Immunocytochemical characterization of neuronal populations in the subplate and marginal zone. J Comp Neurol. 1994;342:571–95.CrossRefPubMed
12.
Oomen CA, Bekinschtein P, Kent BA, Saksida LM, Bussey TJ. Adult hippocampal neurogenesis and its role in cognition. Wiley Interdiscip Rev Cogn Sci. 2014;5:573–87.CrossRefPubMedPubMedCentral
13.
Committee on the Use of Complementary, and Alternative Medicine by the American Public Board on Health Promotion Disease Prevention Institute of Medicine. Complementary and Alternative Medicine in the United States. Washington DC: The National Academies Press; 2005.
14.
Braun LA, Tiralongo E, Wilkinson JM, Spitzer O, Bailey M, Poole S, Dooley M. Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice. BMC Complement Altern Med. 2010;10:38.CrossRefPubMedPubMedCentral
15.
Park BY, Min BS, Oh SR, Kim JH, Kim TJ, Kim DH, Bae KH, Lee HK. Isolation and anticomplement activity of compounds from Dendropanax morbifera. J Ethnopharmacol. 2004;90:403–8.CrossRefPubMed
16.
Park SY, Karthivashan G, Ko HM, Cho DY, Kim J, Cho DJ, Ganesan P, Su-Kim I, Choi DK. Aqueous extract of Dendropanax morbiferus leaves effectively alleviated neuroinflammation and behavioral impediments in MPTP-induced Parkinson's mouse model. Oxidative Med Cell Longev. 2018;2018:3175214.
17.
Lee KY, Jung HY, Yoo DY, Kim W, Kim JW, Kwon HJ, Kim DW, Yoon YS, Hwang IK, Choi JH. Dendropanax morbifera Léveille extract ameliorates D-galactose-induced memory deficits by decreasing inflammatory responses in the hippocampus. Lab Anim Res. 2017;33:283–90.CrossRefPubMedPubMedCentral
18.
Kim W, Kim DW, Yoo DY, Jung HY, Nam SM, Kim JW, Hong SM, Kim DW, Choi JH, Moon SM, Yoon YS, Hwang IK. Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats. BMC Complement Altern Med. 2014;14:428.CrossRefPubMedPubMedCentral
19.
Kim W, Kim DW, Yoo DY, Jung HY, Kim JW, Kim DW, Choi JH, Moon SM, Yoon YS, Hwang IK. Antioxidant effects of Dendropanax morbifera Léveille extract in the hippocampus of mercury-exposed rats. BMC Complement Altern Med. 2015;15:247.CrossRefPubMedPubMedCentral
20.
Kim W, Yim HS, Yoo DY, Jung HY, Kim JW, Choi JH, Yoon YS, Kim DW, Hwang IK. Dendropanax morbifera Léveille extract ameliorates cadmium-induced impairment in memory and hippocampal neurogenesis in rats. BMC Complement Altern Med. 2016;16:452.CrossRefPubMedPubMedCentral
21.
Choo GS, Lim DP, Kim SM, Yoo ES, Kim SH, Kim CH, Woo JS, Kim HJ, Jung JY. Anti-inflammatory effects of Dendropanax morbifera in lipopolysaccharide-stimulated RAW264.7 macrophages and in an animal model of atopic dermatitis. Mol Med Rep. 2019;19:2087–96.PubMedPubMedCentral
22.
Seo JS, Yoo DY, Jung HY, Kim DW, Hwang IK, Lee JY, Moon SM. Effects of Dendropanax morbifera Léveille extracts on cadmium and mercury secretion as well as oxidative capacity: a randomized, double-blind, placebo-controlled trial. Biomed Rep. 2016;4:623–7.CrossRefPubMedPubMedCentral
23.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412.CrossRefPubMedPubMedCentral
24.
Hyun TK, Ko YJ, Kim EH, Chung IM, Kim JS. Anti-inflammatory activity and phenolic composition of Dendropanx morbifera leaf extracts. Ind Crop Prod. 2015;74:263–70.CrossRef
25.
Yoo DY, Woo YJ, Kim W, Nam SM, Lee BH, Yeun GH, Yoon YS, Won MH, Park JH, Hwang IK. Effects of a new synthetic butyrylcholinesterase inhibitor, HBU-39, on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model. Neurochem Int. 2011;59:722–8.CrossRefPubMed
26.
Yoo DY, Choi JH, Kim W, Nam SM, Jung HY, Kim JH, Won MH, Yoon YS, Hwang IK. Effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia model. Neurol Res. 2013;35:813–20.CrossRefPubMed
27.
Nam SM, Kim JW, Yoo DY, Jung HY, Chung JY, Kim DW, Hwang IK, Yoon YS. Hypothyroidism increases cyclooxygenase-2 levels and pro-inflammatory response and decreases cell proliferation and neuroblast differentiation in the hippocampus. Mol Med Rep. 2018;17:5782–8.PubMedPubMedCentral
28.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Amsterdam: Elsevier Academic Press; 2007.
29.
Nagy A, Delgado-Escueta AV. Rapid preparation of synaptosomes from mammalian brain using nontoxic isoosmotic gradient material (Percoll). J Neurochem. 1984;43:1114–23.CrossRefPubMed
30.
Rocha JB, Emanuelli T, Pereira ME. Effects of early undernutrition on kinetic parameters of brain acetylcholinesterase from adult rats. Acta Neurobiol Exp (Wars). 1993;53:431–7.
31.
Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, Murata K, Sørensen N, Dahl R, Jørgensen PJ. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol. 1997;19:417–28.CrossRefPubMed
32.
Graeme KA, Pollack CV Jr. Heavy metal toxicity, part I: arsenic and mercury. J Emerg Med. 1998;16:45–56.CrossRefPubMed
33.
Lapham LW, Cernichiari E, Cox C, Myers GJ, Baggs RB, Brewer R, Shamlaye CF, Davidson PW, Clarkson TW. An analysis of autopsy brain tissue from infants prenatally exposed to methymercury. Neurotoxicology. 1995;16:689–704.PubMed
34.
Onishchenko N, Tamm C, Vahter M, Hokfelt T, Johnson JA, Johnson DA, Ceccatelli S. Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice. Toxicol Sci. 2007;97:428–37.CrossRefPubMed
35.
Kim JM, Park SK, Guo TJ, Kang JY, Ha JS, Lee du S, Lee U, Heo HJ. Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice. Behav Brain Res. 2016;312:39–54.CrossRefPubMed
36.
Aizawa K, Ageyama N, Yokoyama C, Hisatsune T. Age-dependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys. Exp Anim. 2009;58:403–7.CrossRefPubMed
37.
Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, Fike JR. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol. 2004;188:316–30.CrossRefPubMed
38.
Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM. A role for adult neurogenesis in spatial long-term memory. Neuroscience. 2005;130:843–52.CrossRefPubMed
39.
Sokolowski K, Obiorah M, Robinson K, McCandlish E, Buckley B, DiCicco-Bloom E. Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits. Dev Neurobiol. 2013;73:936–49.CrossRefPubMed
40.
Moretto MB, Lermen CL, Morsch VM, Bohrer D, Ineu RP, da Silva AC, Balz D, Schetinger MR. Effect of subchronic treatment with mercury chloride on NTPDase, 5′-nucleotidase and acetylcholinesterase from cerebral cortex of rats. J Trace Elem Med Biol. 2004;17:255–60.CrossRefPubMed
41.
Taupin P. Adult neurogenesis and neural stem cells as a model for the discovery and development of novel drugs. Expert Opin Drug Discov. 2010;5:921–5.CrossRefPubMed
42.
Kita Y, Ago Y, Higashino K, Asada K, Takano E, Takuma K, Matsuda T. Galantamine promotes adult hippocampal neurogenesis via M1 muscarinic and α7 nicotinic receptors in mice. Int J Neuropsychopharmacol. 2014;17:1957–68.CrossRefPubMed
43.
Kwon KJ, Kim MK, Lee EJ, Kim JN, Choi BR, Kim SY, Cho KS, Han JS, Kim HY, Shin CY, Han SH. Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia. J Neurol Sci. 2014;347:66–77.CrossRefPubMed
44.
Girard C, Charette T, Leclerc M, Shapiro BJ, Amyot M. Cooking and co-ingested polyphenols reduce in vitro methylmercury bioaccessibility from fish and may alter exposure in humans. Sci Total Environ. 2018;616-617:863–74.CrossRefPubMed
45.
Wang X, Fan X, Yuan S, Jiao W, Liu B, Cao J, Jiang W. Chlorogenic acid protects against aluminium-induced cytotoxicity through chelation and antioxidant actions in primary hippocampal neuronal cells. Food Funct. 2017;8:2924–34.CrossRefPubMed
46.
Kwon SH, Lee HK, Kim JA, Hong SI, Kim HC, Jo TH, Park YI, Lee CK, Kim YB, Lee SY, Jang CG. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur J Pharmacol. 2010;649:210–7.CrossRefPubMed
47.
Choi HJ, Park DH, Song SH, Yoon IS, Cho SS. Development and validation of a HPLC-UV method for extraction optimization and biological evaluation of hot-water and ethanolic extracts of Dendropanax morbifera leaves. Molecules. 2018;23:E650.CrossRefPubMed
48.
Franco JL, Posser T, Missau F, Pizzolatti MG, Dos Santos AR, Souza DO, Aschner M, Rocha JB, Dafre AL, Farina M. Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction. Environ Toxicol Pharmacol. 2010;30:272–8.CrossRefPubMedPubMedCentral
Metadata
Title
Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus
Authors
Woosuk Kim
Dae Young Yoo
Hyo Young Jung
Jong Whi Kim
Kyu Ri Hahn
Hyun Jung Kwon
Miyoung Yoo
Sanghee Lee
Sung Min Nam
Yeo Sung Yoon
Dae Won Kim
In Koo Hwang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2508-6

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