{"corpus_id":17844721,"paper_sha":null,"doi":"10.1186/s13195-016-0206-x","arxiv_id":null,"pmid":27630117,"pmcid":"5024520","mag_id":2518763897,"dblp_id":null,"acl_id":null,"title":"Protective effect of melatonin on soluble Aβ1–42-induced memory impairment, astrogliosis, and synaptic dysfunction via the Musashi1/Notch1/Hes1 signaling pathway in the rat hippocampus","year":2016,"publication_date":"2016-09-15","venue":"Alzheimer's Research & Therapy","journal":{"name":"Alzheimer's Research & Therapy","pages":null,"volume":"8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":45,"citation_count":69,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Amyloid beta-Peptides","mj":false,"qs":[{"q":"toxicity","mj":true,"ui":"Q000633"}],"ui":"D016229"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Behavior, Animal","mj":false,"ui":"D001522"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Gliosis","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"}],"ui":"D005911"},{"d":"Hippocampus","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D006624"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Melatonin","mj":false,"qs":[{"q":"administration & dosage","mj":false,"ui":"Q000008"},{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D008550"},{"d":"Memory Disorders","mj":false,"qs":[{"q":"chemically induced","mj":false,"ui":"Q000139"},{"q":"drug therapy","mj":true,"ui":"Q000188"}],"ui":"D008569"},{"d":"Nerve Tissue Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D009419"},{"d":"Neuronal Plasticity","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D009473"},{"d":"Neuroprotective Agents","mj":false,"qs":[{"q":"administration & dosage","mj":false,"ui":"Q000008"},{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D018696"},{"d":"Peptide Fragments","mj":false,"qs":[{"q":"toxicity","mj":true,"ui":"Q000633"}],"ui":"D010446"},{"d":"RNA-Binding Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D016601"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Receptor, Notch1","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D051881"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D015398"},{"d":"Spatial Learning","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D065853"},{"d":"Transcription Factor HES-1","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D000072056"}],"chemicals":[{"n":"Amyloid beta-Peptides","ui":"D016229","reg":"0"},{"n":"Hes1 protein, rat","ui":"C489735","reg":"0"},{"n":"Msi1 protein, rat","ui":"C491296","reg":"0"},{"n":"Nerve Tissue Proteins","ui":"D009419","reg":"0"},{"n":"Neuroprotective Agents","ui":"D018696","reg":"0"},{"n":"Notch1 protein, rat","ui":"C497763","reg":"0"},{"n":"Peptide Fragments","ui":"D010446","reg":"0"},{"n":"RNA-Binding Proteins","ui":"D016601","reg":"0"},{"n":"Receptor, Notch1","ui":"D051881","reg":"0"},{"n":"Transcription Factor HES-1","ui":"D000072056","reg":"0"},{"n":"amyloid beta-protein (1-42)","ui":"C075222","reg":"0"},{"n":"Melatonin","ui":"D008550","reg":"JL5DK93RCL"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-016-0206-x","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/3e6fdec019ed09fc7f889d33adcb0301f8804a8d","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BackgroundAmyloid-beta (Aβ) plays a key role in Alzheimer’s disease (AD) pathogenesis, and soluble Aβ oligomers are more cytotoxic than Aβ fibrils. Recent evidence suggests that Notch signaling is affected by AD and other brain diseases. Melatonin exerts beneficial effects on many aspects of AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1–42.MethodsAn AD rat model was established via repeated intracerebroventricular administration of soluble Aβ1–42. Melatonin treatment was administered 24 hours prior to Aβ1–42 administration via an intraperitoneal injection. The effects of melatonin on spatial learning and memory, synaptic plasticity, and astrogliosis were investigated. The expression of several Notch1 signaling components, including Notch1, the Notch1 intracellular domain (NICD), Hairy and enhancer of split 1 (Hes1, a downstream effector of Notch), and Musashi1 (a positive regulator of Notch), were examined using immunohistochemistry, western blotting, and quantitative real-time PCR. In vitro studies were conducted to determine whether the melatonin-mediated protection against Aβ1–42 was inhibited by DAPT, an inhibitor of Notch signaling.ResultsMelatonin improved the Aβ1–42-induced impairment in spatial learning and memory, attenuated synaptic dysfunction, and reduced astrogliosis. Melatonin also ameliorated the effects of Aβ1–42 on Notch1, NICD, Hes1, and Musashi1. The in vitro studies demonstrated that DAPT effectively blocked the neuroprotective effect of melatonin against Aβ1–42.ConclusionsThese findings suggest that melatonin may improve the soluble Aβ1–42-induced impairment of spatial learning and memory, synaptic plasticity, and astrogliosis via the Musashi1/Notch1/Hes1 signaling pathway.","claims":[{"public_id":"cl_a91b2eb84ea98a51c6b9ba39a9eb4d1b","status":"active","text":"DAPT blocks the neuroprotective effect of melatonin against Aβ1–42 in vitro, supporting involvement of Notch signaling in the protection.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_a91b2eb84ea98a51c6b9ba39a9eb4d1b"},{"public_id":"cl_fdb7f93b40a135f7a156296ac44913be","status":"active","text":"Melatonin ameliorates the Aβ1–42-induced changes in Notch1, NICD, Hes1, and Musashi1 expression.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_fdb7f93b40a135f7a156296ac44913be"},{"public_id":"cl_53ff47acb68c2a7b64bb0945d5864f60","status":"active","text":"Melatonin attenuates soluble Aβ1–42-induced synaptic dysfunction and astrogliosis.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_53ff47acb68c2a7b64bb0945d5864f60"},{"public_id":"cl_8f4316bee2d8d309a746607ab07bde7e","status":"active","text":"Melatonin improves soluble Aβ1–42-induced impairment of spatial learning and memory in the rat hippocampus.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8f4316bee2d8d309a746607ab07bde7e"}],"concepts":[{"public_id":"co_0de4a13197ab9c6711b5a3d2d8c38c5b","status":"active","name":"Notch signaling","description":"A cell-signaling pathway implicated here in melatonin-mediated neuroprotection.","types":["signaling pathway"],"aliases":["Notch1 signaling"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0de4a13197ab9c6711b5a3d2d8c38c5b"},{"public_id":"co_390b91257549d636ce002382b5af8114","status":"active","name":"rat hippocampus","description":"The brain region in rats where the model and molecular measurements were performed.","types":["anatomical structure","experimental tissue"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_390b91257549d636ce002382b5af8114"},{"public_id":"co_4d427178daae2cfc065cbb128c1a3be2","status":"active","name":"Notch1 signaling components","description":"Proteins measured in the Notch1 pathway, including Notch1, NICD, Hes1, and Musashi1.","types":["molecular pathway component"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4d427178daae2cfc065cbb128c1a3be2"},{"public_id":"co_6c28e5974597d1be180ad6f4a766ff14","status":"active","name":"melatonin","description":"An endogenous hormone used here as a treatment to test neuroprotective effects.","types":["compound","treatment"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6c28e5974597d1be180ad6f4a766ff14"},{"public_id":"co_8277234d95751b0b43b3a7f9cfcec05c","status":"active","name":"soluble Aβ1–42","description":"A soluble amyloid-beta 1–42 peptide preparation used to induce Alzheimer-like brain injury.","types":["peptide","disease model agent"],"aliases":["Aβ1–42","soluble Aβ oligomers"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8277234d95751b0b43b3a7f9cfcec05c"},{"public_id":"co_a7d2c5fde4b1e37cede03f8a1a56d5c0","status":"active","name":"synaptic dysfunction","description":"Impaired synaptic function or plasticity in the hippocampus.","types":["outcome","neurological dysfunction"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a7d2c5fde4b1e37cede03f8a1a56d5c0"},{"public_id":"co_a9c6c67219b58e9b33e2b6bb43d00fa8","status":"active","name":"spatial learning and memory","description":"Cognitive abilities related to acquiring and recalling spatial information.","types":["outcome","cognitive function"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a9c6c67219b58e9b33e2b6bb43d00fa8"},{"public_id":"co_c405d20a9770d26cc871cdfe1b4cfb12","status":"active","name":"DAPT","description":"A pharmacological inhibitor of Notch signaling used to test pathway dependence.","types":["inhibitor","compound"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_c405d20a9770d26cc871cdfe1b4cfb12"},{"public_id":"co_e4b9b264c206e64ad8c78deff2847e15","status":"active","name":"Musashi1/Notch1/Hes1 signaling pathway","description":"A signaling axis linking Musashi1, Notch1 activation, and the downstream effector Hes1.","types":["signaling pathway"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e4b9b264c206e64ad8c78deff2847e15"},{"public_id":"co_e8ce145b2ebf9dec6a9da70018165b40","status":"active","name":"astrogliosis","description":"Reactive changes in astrocytes associated with brain injury or disease.","types":["cellular response","pathological process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e8ce145b2ebf9dec6a9da70018165b40"}],"external_ids":{"DOI":"10.1186/s13195-016-0206-x","ArXiv":null,"PubMed":27630117,"PubMedCentral":"5024520","MAG":2518763897,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-016-0206-x","landing_url":"https://www.semanticscholar.org/paper/3e6fdec019ed09fc7f889d33adcb0301f8804a8d","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBY","status":"GOLD","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631117,"paper_uid":"81e2224a-2b43-4049-b1b3-ab25f0e677c1","canonical_identity":{"paper_id":631117,"paper_uid":"81e2224a-2b43-4049-b1b3-ab25f0e677c1","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/17844721"}