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      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

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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.

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          Most cited references42

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          A role for adult neurogenesis in spatial long-term memory.

          Adult hippocampal neurogenesis has been linked to learning but details of the relationship between neuronal production and memory formation remain unknown. Using low dose irradiation to inhibit adult hippocampal neurogenesis we show that new neurons aged 4-28 days old at the time of training are required for long-term memory in a spatial version of the water maze. This effect of irradiation was specific since long-term memory for a visibly cued platform remained intact. Furthermore, irradiation just before or after water maze training had no effect on learning or long-term memory. Relationships between learning and new neuron survival, as well as proliferation, were investigated but found non-significant. These results suggest a new role for adult neurogenesis in the formation and/or consolidation of long-term, hippocampus-dependent, spatial memories.
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            Cognitive Deficit in 7-Year-Old Children with Prenatal Exposure to Methylmercury

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              Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice.

              Advances in the management of pediatric brain tumors have increased survival rates in children, but their quality of life is impaired due to cognitive deficits that arise from irradiation. The pathogenesis of these deficits remains unknown, but may involve reduced neurogenesis within the hippocampus. To determine the acute radiosensitivity of the dentate subgranular zone (SGZ), 21-day-old C57BL/J6 male mice received whole brain irradiation (2-10 Gy), and 48 h later, tissue was assessed using immunohistochemistry. Proliferating SGZ cells and their progeny, immature neurons, were decreased in a dose-dependent fashion. To determine if acute changes translated into long-term alterations in neurogenesis, mice were given a single dose of 5 Gy, and 1 or 3 months later, proliferating cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Confocal microscopy was used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes. X-rays significantly reduced the production of new neurons at both time points, while glial components showed no change or small increases. Measures of activated microglia and infiltrating, peripheral monocytes indicated that reduced neurogenesis was associated with a chronic inflammatory response. Three months after irradiation, changes in neurogenesis were associated with spatial memory retention deficits determined using the Morris water maze. Behavioral training and testing increased the numbers of immature neurons, most prominently in irradiated animals. These data provide evidence that irradiation of young animals induces a long-term impairment of SGZ neurogenesis that is associated with hippocampal-dependent memory deficits.
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                Author and article information

                Contributors
                tank3430@snu.ac.kr
                dyyoo@sch.ac.kr
                hyoyoung@snu.ac.kr
                kimjongwhi@snu.ac.kr
                hkinging@snu.ac.kr
                donuts25@gwnu.ac.kr
                myyoo@kfri.re.kr
                shlee@kfri.re.kr
                lovingvet@gmail.com
                ysyoon@snu.ac.kr
                kimdw@gwnu.ac.kr
                vetmed2@snu.ac.kr
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                2 May 2019
                2 May 2019
                2019
                : 19
                : 94
                Affiliations
                [1 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, , Seoul National University, ; Seoul, 08826 South Korea
                [2 ]ISNI 0000 0004 1773 6524, GRID grid.412674.2, Department of Anatomy, College of Medicine, , Soonchunhyang University, ; Cheonan, Chungcheongnam 31151 South Korea
                [3 ]ISNI 0000 0004 0532 811X, GRID grid.411733.3, Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, , Gangneung-Wonju National University, ; Gangneung, 25457 South Korea
                [4 ]ISNI 0000 0001 0573 0246, GRID grid.418974.7, Korea Food Research Institute, ; Jeollabuk-do, 55365 South Korea
                [5 ]ISNI 0000 0004 0532 8339, GRID grid.258676.8, Department of Anatomy, College of Veterinary Medicine, , Konkuk University, ; Seoul, 05030 South Korea
                Author information
                http://orcid.org/0000-0002-0533-4638
                Article
                2508
                10.1186/s12906-019-2508-6
                6498467
                31046739
                e6623820-f7e2-4abd-9c71-bd316cac2490
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 September 2018
                : 17 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002701, Ministry of Education;
                Award ID: NRF-2016R1A2B4009156
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Complementary & Alternative medicine
                dendropanax morbifera extract,mercury,morris water maze,neurogenesis,hippocampus

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