Effects of NK-4 in a Transgenic Mouse Model of Alzheimer's Disease
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{"title"=>"Effects of NK-4 in a transgenic mouse model of alzheimer's disease", "type"=>"journal", "authors"=>[{"first_name"=>"Hitomi", "last_name"=>"Ohta", "scopus_author_id"=>"14042539000"}, {"first_name"=>"Shigeyuki", "last_name"=>"Arai", "scopus_author_id"=>"7401693727"}, {"first_name"=>"Kenji", "last_name"=>"Akita", "scopus_author_id"=>"7102851336"}, {"first_name"=>"Tsunetaka", "last_name"=>"Ohta", "scopus_author_id"=>"7403162078"}, {"first_name"=>"Shigeharu", "last_name"=>"Fukuda", "scopus_author_id"=>"7403146085"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84855374955", "doi"=>"10.1371/journal.pone.0030007", "sgr"=>"84855374955", "pmid"=>"22238689", "issn"=>"19326203", "pui"=>"364037772"}, "id"=>"e653acf1-9259-3a30-9d5a-a2e46ecafc79", "abstract"=>"Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and molecules that can prevent pathways of Aβ toxicity may be potential therapeutic agents for treatment of AD. We have previously reported that NK-4, a cyanine photosensitizing dye, displays neurotrophic and antioxidant activities. In this study, we report the effects of NK-4 on the toxicity of Aβ and on cognitive function and Aβ concentration in a transgenic mouse model of AD (Tg2576). In vitro, NK-4 effectively protected neuronal cells from toxicity induced by Aβ. In addition, it displayed profound inhibitory activities on Aβ fibril formation. In vivo, Tg2576 mice received an intraperitoneal injection at 100 or 500 µg/kg of NK-4 once a day, five times a week for 9 months. Administration of NK-4 to the mice attenuated impairment of recognition memory, associative memory, and learning ability, as assessed by a novel object recognition test, a passive avoidance test, and a water maze test, respectively. NK-4 decreased the brain Aβ concentration while increasing the plasma amyloid level in a dose-dependent manner. NK-4 also improved memory impairments of ICR mice induced by direct intracerebroventricular administration of Aβ. These lines of evidence suggest that NK-4 may affect multiple pathways of amyloid pathogenesis and could be useful for treatment of AD.", "link"=>"http://www.mendeley.com/research/effects-nk4-transgenic-mouse-model-alzheimers-disease", "reader_count"=>7, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>1, "Student > Master"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>1, "Student > Master"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Psychology"=>1, "Sports and Recreations"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Egypt"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/696660"], "description"=>"<p>PC12 cells were treated with 50 µM Aβ<sub>25–35</sub> for 72 hr in the absence (open bar) or presence of the indicated concentrations of NK-4 (closed bars). Control cells were incubated under the same conditions, but without Aβ<sub>25–35</sub>. Cell viability was assessed by alamarBlue assay. Results are shown as means ± SD (n = 3). **P<0.01 vs. no NK-4.</p>", "links"=>[], "tags"=>["nk-4", "cytotoxicity", "pc12"], "article_id"=>367060, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytoprotective_effects_of_NK_4_on_A_25_8211_35_induced_cytotoxicity_in_PC12_cells_/367060", "title"=>"Cytoprotective effects of NK-4 on Aβ<sub>25–35</sub>-induced cytotoxicity in PC12 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:17:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/696729"], "description"=>"<p>100 µM of Aβ<sub>1–40</sub> (a, b) or Aβ<sub>1–42</sub> (c, d) was incubated for 72 hr alone (a, c) or with NK-4 (10 µM) (b, d). Bar represents 200 nm. The experiment was performed three times with similar results. (e) Thioflavin T assay of Aβ fibril formation. Three forms of Aβ peptide (Aβ<sub>1–40</sub>, Aβ<sub>1–42</sub> and Aβ<sub>25–35</sub>) were incubated for 72 hr with the indicated concentration of NK-4. Values are means ± SD (n = 3). **P<0.01 vs. control (without NK-4).</p>", "links"=>[], "tags"=>["nk-4", "fibril"], "article_id"=>367142, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_NK_4_on_A_946_fibril_formation_/367142", "title"=>"Effects of NK-4 on Aβ fibril formation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:17:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/696822"], "description"=>"<p>A low (100 µg/kg) or high (500 µg/kg) dose of NK-4 was administered intraperitoneally to female Tg2576 mice from 3 to 12 months of age. Mice were tested for object recognition at 6 and 12 months of age. Values are means ± SEM (n = 10). **P<0.01 vs. saline-treated Tg2576 group. Wild: non-transgenic female 129S6 mice. Tg2576 (saline): saline-treated Tg2576 mice. Tg2576 (NK-4l): low-dose NK-4-treated Tg2576 mice. Tg2576 (NK-4h); high-dose NK-4-treated Tg2576 mice.</p>", "links"=>[], "tags"=>["nk-4", "tg2576", "mice"], "article_id"=>367229, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_NK_4_on_cognitive_function_of_Tg2576_mice_in_a_novel_object_recognition_test_/367229", "title"=>"Effects of NK-4 on cognitive function of Tg2576 mice in a novel object recognition test.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/696900"], "description"=>"<p>Mice were tested for learning ability at 6 and 12 months of age. The mean latency represents the time spent finding a hidden platform placed in a fixed location in the pool. Two trials per day were conducted for 4 consecutive days. Data are expressed as means ± SEM of the averaged time on each day (n = 10). *P<0.05, **P<0.01 vs. saline-treated Tg2576 group.</p>", "links"=>[], "tags"=>["nk-4", "tg2576", "mice", "maze"], "article_id"=>367312, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_NK_4_on_learning_ability_of_Tg2576_mice_in_a_water_maze_test_/367312", "title"=>"Effect of NK-4 on learning ability of Tg2576 mice in a water maze test.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:18:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/696984"], "description"=>"<p>Mice were tested for learning at 9 months of age. The latency in the retention session performed 24 hr after the training session is shown. Values are means ± SEM (n = 10). **P<0.01 vs. saline-treated Tg2576 group.</p>", "links"=>[], "tags"=>["nk-4", "tg2576", "mice", "passive", "avoidance"], "article_id"=>367388, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_NK_4_on_cognitive_function_of_Tg2576_mice_in_a_passive_avoidance_test_/367388", "title"=>"Effect of NK-4 on cognitive function of Tg2576 mice in a passive avoidance test.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:18:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/697065"], "description"=>"<p>NK-4 did not interfere the optical density of both hAβ<sub>1–40</sub> (a) and hAβ<sub>1–42</sub> (b) ELISA systems, which using the antibody combinations of BAN50/BA27 and BAN50/BC05, respectively. Since these ELISA systems cannot distinguish N-terminal heterogeneity of Aβ peptides derived from biological samples, we represented hAβ species as hAβ<sub>x-40</sub> and hAβ<sub>x-42</sub>, respectively. Plasma from mice aged 12 months was used for measurements of hAβ<sub>x-40</sub> (c) and hAβ<sub>x-42</sub> (d). Values are the mean ± SEM for saline-treated Tg2576 mice (control group, n = 10), a low dose NK-4 (100 µg/kg)-treated group (n = 9), and a high dose NK-4 (500 µg/kg)-treated group (n = 8). **P<0.01 vs. saline-treated Tg2576 group.</p>", "links"=>[], "tags"=>["nk-4", "plasma", "concentrations", "tg2576"], "article_id"=>367473, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_NK_4_on_the_plasma_A_946_concentrations_in_Tg2576_mice_/367473", "title"=>"Effect of NK-4 on the plasma Aβ concentrations in Tg2576 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:19:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/697172"], "description"=>"<p>Brains from mice aged 12 months were homogenized and separated into soluble (c, d) and insoluble (a, b) fractions of Aβ, and assayed for hAβ<sub>x-40</sub> (a, c) and hAβ<sub>x-42</sub> (b, d), respectively. FA: SDS insoluble and formic acid soluble fractions of Aβ. SDS: SDS soluble fractions of Aβ. Correlations are shown between the plasma and brain levels of hAβ<sub>x-40</sub> (e) and hAβ<sub>x-42</sub> (f) in Tg2576 mice. Data are the mean ± SEM of hAβ<sub>x-40</sub> or hAβ<sub>x-42</sub> in each mouse in saline-treated Tg2576 controls (n = 10), a low dose NK-4 (100 µg/kg)-treated group (n = 9), and a high dose NK-4 (500 µg/kg)-treated group (n = 8). *P<0.05, **P<0.01 vs. saline-treated Tg2576 group.</p>", "links"=>[], "tags"=>["nk-4", "soluble", "insoluble", "tg2576"], "article_id"=>367579, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_NK_4_on_brain_soluble_or_insoluble_A_x_40_and_A_946_x_42_in_Tg2576_mice_/367579", "title"=>"Effect of NK-4 on brain soluble or insoluble Aβ<sub>x-40</sub> and Aβ<sub>x-42</sub> in Tg2576 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:19:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/697277"], "description"=>"<p>Coronal brain sections (cortex region) were stained by Congo Red (a) or anti-Aβ polyclonal antibody (b, c). The number of CR-positive plaques on the section was counted in cortex region (a). Typical images of Aβ-immunoreactive tangles of saline-treated Tg2576 mouse (b) and high-dose NK-4(500 µg/kg)-treated Tg2576 mouse (c). Bar represents 50 µm.</p>", "links"=>[], "tags"=>["deposition", "brains", "tg2576", "mice", "12", "months"], "article_id"=>367671, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_946_deposition_in_brains_of_Tg2576_mice_at_12_months_of_age_/367671", "title"=>"Aβ deposition in brains of Tg2576 mice at 12 months of age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:20:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/697373"], "description"=>"<p>Cognitive impairment was induced in ICR mice by icv injection of Aβ<sub>25–35</sub> solution as described in Material and Method. A low (50 µg/kg) or high (500 µg/kg) dose of NK-4 was administered intraperitoneally to mice twelve consecutive days starting from the next day of Aβ injection (day1). Mice were tested for object recognition (a), followed by passive avoidance (b). Values are means ± SEM (n = 10). Sham: sham-operated group, saline: saline-treated Aβ<sub>25–35</sub>–icv group, NK-4l: low-dose NK-4-treated Aβ<sub>25–35</sub>–icv group, NK-4h; high-dose NK-4-treated Aβ<sub>25–35</sub>–icv group. *P<0.05, **P<0.01 vs. saline-treated group.</p>", "links"=>[], "tags"=>["nk-4", "impairments", "icr"], "article_id"=>367770, "categories"=>["Neuroscience"], "users"=>["Hitomi Ohta", "Shigeyuki Arai", "Kenji Akita", "Tsunetaka Ohta", "Shigeharu Fukuda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030007.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_NK_4_on_A_25_8211_35_induced_cognitive_impairments_in_ICR_Mice_/367770", "title"=>"Effects of NK-4 on Aβ<sub>25–35</sub>-induced cognitive impairments in ICR Mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:20:54"}

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Relative Metric

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