SKF83959 Has Protective Effects in the Scopolamine Model of Dementia
Patients with Alzheimer’s disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to i...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2018/03/01, Vol.41(3), pp.427-434 |
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| creator | Sheng, Gaofeng Zhang, Jinlin Gao, Shengfeng Gu, Yuanyuan Jiang, Bo Gao, Qiufang |
| description | Patients with Alzheimer’s disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD. |
| doi_str_mv | 10.1248/bpb.b17-00877 |
| format | Article |
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In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b17-00877</identifier><identifier>PMID: 29491219</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - analogs & derivatives ; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - therapeutic use ; Alzheimer's disease ; Amnesia - chemically induced ; Amnesia - drug therapy ; Amnesia - psychology ; Animals ; Avoidance Learning - drug effects ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - drug effects ; Carbazoles - pharmacology ; Chemical compounds ; Cognitive ability ; Dementia ; Dementia - chemically induced ; Dementia - drug therapy ; Dementia - psychology ; Dementia disorders ; Enzyme inhibitors ; Hippocampus ; Hippocampus - drug effects ; Indole Alkaloids - pharmacology ; Male ; Maze Learning - drug effects ; memory ; Memory - drug effects ; Mental task performance ; Mice ; Mice, Inbred ICR ; Muscarinic Antagonists ; Protein-tyrosine kinase ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Psychomotor Performance - drug effects ; Scopolamine ; Scopolamine Hydrobromide ; Signal Transduction - drug effects ; SKF83959 ; TrkB receptors ; Water treatment ; Western blotting</subject><ispartof>Biological and Pharmaceutical Bulletin, 2018/03/01, Vol.41(3), pp.427-434</ispartof><rights>2018 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-2d1ab66ec4577c48077ffd5fbb403c862988249e2d2e088118804ab4c11fef9e3</citedby><cites>FETCH-LOGICAL-c702t-2d1ab66ec4577c48077ffd5fbb403c862988249e2d2e088118804ab4c11fef9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27902,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29491219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheng, Gaofeng</creatorcontrib><creatorcontrib>Zhang, Jinlin</creatorcontrib><creatorcontrib>Gao, Shengfeng</creatorcontrib><creatorcontrib>Gu, Yuanyuan</creatorcontrib><creatorcontrib>Jiang, Bo</creatorcontrib><creatorcontrib>Gao, Qiufang</creatorcontrib><creatorcontrib>The Second Affiliated Hospital of Nantong University</creatorcontrib><creatorcontrib>The Third Affiliated Hospital of Nantong University</creatorcontrib><creatorcontrib>aDepartment of Pharmacy</creatorcontrib><creatorcontrib>cDepartment of Pharmacology</creatorcontrib><creatorcontrib>School of Pharmacy</creatorcontrib><creatorcontrib>Affiliated Cancer Hospital of Nantong University</creatorcontrib><creatorcontrib>bDepartment of Pharmacy</creatorcontrib><creatorcontrib>and (dDepartment of Pharmacy</creatorcontrib><creatorcontrib>Nantong University</creatorcontrib><title>SKF83959 Has Protective Effects in the Scopolamine Model of Dementia</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Patients with Alzheimer’s disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.</description><subject>2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - analogs & derivatives</subject><subject>2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - therapeutic use</subject><subject>Alzheimer's disease</subject><subject>Amnesia - chemically induced</subject><subject>Amnesia - drug therapy</subject><subject>Amnesia - psychology</subject><subject>Animals</subject><subject>Avoidance Learning - drug effects</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - drug effects</subject><subject>Carbazoles - pharmacology</subject><subject>Chemical compounds</subject><subject>Cognitive ability</subject><subject>Dementia</subject><subject>Dementia - chemically induced</subject><subject>Dementia - drug therapy</subject><subject>Dementia - psychology</subject><subject>Dementia disorders</subject><subject>Enzyme inhibitors</subject><subject>Hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Indole Alkaloids - pharmacology</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>memory</subject><subject>Memory - drug effects</subject><subject>Mental task performance</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Muscarinic Antagonists</subject><subject>Protein-tyrosine kinase</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Psychomotor Performance - drug effects</subject><subject>Scopolamine</subject><subject>Scopolamine Hydrobromide</subject><subject>Signal Transduction - drug effects</subject><subject>SKF83959</subject><subject>TrkB receptors</subject><subject>Water treatment</subject><subject>Western blotting</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1v1DAURS0EokNhyRZFYsMm7Xu2E9tLNP1CFLVSYW05zjPNyImHOIPEv8ftlEHqxrbko3uvDmPvEU6QS33abbuTDlUNoJV6wVYopKobjs1LtgKDum6x0UfsTc4bAFDAxWt2xI00yNGs2Nnd1wstTGOqK5er2zkt5JfhN1XnIZRXroapWu6puvNpm6Ibh4mqb6mnWKVQndFI0zK4t-xVcDHTu6f7mP24OP--vqqvby6_rD9f1770LjXv0XVtS142SnmpQakQ-iZ0nQThdcuN1lwa4j0n0BpRa5Cukx4xUDAkjtmnfe52Tr92lBc7DtlTjG6itMuWA5imbVUrC_rxGbpJu3kq6yznEgVvGykKVe8pP6ecZwp2Ow-jm_9YBPug1xa9tui1j3oL_-EpddeN1B_ofz4LcLkHyu_gXUxTLMb-d_usuiHFVKaiLqESQVhAY0HyUiKFFCBKEZSk9T5pkxf3kw5Vbl4GH-lxmEQrHo7DwMOvv3ezpUn8Ba7woL8</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Sheng, Gaofeng</creator><creator>Zhang, Jinlin</creator><creator>Gao, Shengfeng</creator><creator>Gu, Yuanyuan</creator><creator>Jiang, Bo</creator><creator>Gao, Qiufang</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>2018</creationdate><title>SKF83959 Has Protective Effects in the Scopolamine Model of Dementia</title><author>Sheng, Gaofeng ; 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In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>29491219</pmid><doi>10.1248/bpb.b17-00877</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - analogs & derivatives 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - therapeutic use Alzheimer's disease Amnesia - chemically induced Amnesia - drug therapy Amnesia - psychology Animals Avoidance Learning - drug effects Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - drug effects Carbazoles - pharmacology Chemical compounds Cognitive ability Dementia Dementia - chemically induced Dementia - drug therapy Dementia - psychology Dementia disorders Enzyme inhibitors Hippocampus Hippocampus - drug effects Indole Alkaloids - pharmacology Male Maze Learning - drug effects memory Memory - drug effects Mental task performance Mice Mice, Inbred ICR Muscarinic Antagonists Protein-tyrosine kinase Protein-Tyrosine Kinases - antagonists & inhibitors Psychomotor Performance - drug effects Scopolamine Scopolamine Hydrobromide Signal Transduction - drug effects SKF83959 TrkB receptors Water treatment Western blotting |
| title | SKF83959 Has Protective Effects in the Scopolamine Model of Dementia |
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