{"corpus_id":52820062,"paper_sha":"49031ff01e594d8e11f709ea495b9d64543b0ceb","doi":"10.1371/journal.pone.0170083","arxiv_id":null,"pmid":28076448,"pmcid":"5226784","mag_id":2572335422,"dblp_id":null,"acl_id":null,"title":"IGF-1 Induces GHRH Neuronal Axon Elongation during Early Postnatal Life in Mice","year":2017,"publication_date":"2017-01-11","venue":"PLoS ONE","journal":{"name":"PLoS ONE","pages":null,"volume":"12"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":43,"citation_count":25,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Animals, Newborn","mj":false,"ui":"D000831"},{"d":"Axons","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D001369"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Growth Hormone-Releasing Hormone","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D013007"},{"d":"Growth and Development","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D048788"},{"d":"Insulin-Like Growth Factor I","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D007334"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred C57BL","mj":false,"ui":"D008810"},{"d":"Mice, Transgenic","mj":false,"ui":"D008822"},{"d":"Neuronal Outgrowth","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D000071446"},{"d":"Neurons","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D009474"}],"chemicals":[{"n":"Insulin-Like Growth Factor I","ui":"D007334","reg":"67763-96-6"},{"n":"Growth Hormone-Releasing Hormone","ui":"D013007","reg":"9034-39-3"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0170083&type=printable","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/49031ff01e594d8e11f709ea495b9d64543b0ceb","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":"Nutrition during the perinatal period programs body growth. Growth hormone (GH) secretion from the pituitary regulates body growth and is controlled by Growth Hormone Releasing Hormone (GHRH) neurons located in the arcuate nucleus of the hypothalamus. We observed that dietary restriction during the early postnatal period (i.e. lactation) in mice influences postnatal growth by permanently altering the development of the somatotropic axis in the pituitary gland. This alteration may be due to a lack of GHRH signaling during this critical developmental period. Indeed, underfed pups showed decreased insulin-like growth factor I (IGF-I) plasma levels, which are associated with lower innervation of the median eminence by GHRH axons at 10 days of age relative to normally fed pups. IGF-I preferentially stimulated axon elongation of GHRH neurons in in vitro arcuate explant cultures from 7 day-old normally fed pups. This IGF-I stimulating effect was selective since other arcuate neurons visualized concomitantly by neurofilament labeling, or AgRP immunochemistry, did not significantly respond to IGF-I stimulation. Moreover, GHRH neurons in explants from age-matched underfed pups lost the capacity to respond to IGF-I stimulation. Molecular analyses indicated that nutritional restriction was associated with impaired activation of AKT. These results highlight a role for IGF-I in axon elongation that appears to be cell selective and participates in the complex cellular mechanisms that link underfeeding during the early postnatal period with programming of the growth trajectory.","claims":[{"public_id":"cl_183b4e3be68667147ca2edfa5d2e0ab1","status":"active","text":"Dietary restriction during the early postnatal period permanently alters somatotropic axis development in mice, influencing postnatal growth.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/claims/cl_183b4e3be68667147ca2edfa5d2e0ab1"},{"public_id":"cl_018c0397eeaf83e448688460b34b8ab1","status":"active","text":"GHRH neurons from underfed pups lose the capacity to respond to IGF-I stimulation, and nutritional restriction is associated with impaired AKT activation.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/claims/cl_018c0397eeaf83e448688460b34b8ab1"},{"public_id":"cl_d80dffd7311c0c12791138201bb56e93","status":"active","text":"IGF-I preferentially stimulates axon elongation of GHRH neurons in in vitro arcuate explant cultures from normally fed pups, and this effect is selective relative to other arcuate neurons.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/claims/cl_d80dffd7311c0c12791138201bb56e93"},{"public_id":"cl_01a7cecb2a397618693d20cf792cd135","status":"active","text":"Underfed pups exhibit decreased IGF-I plasma levels and lower innervation of the median eminence by GHRH axons at 10 days of age compared to normally fed pups.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/claims/cl_01a7cecb2a397618693d20cf792cd135"}],"concepts":[{"public_id":"co_206fbcd6a0fc5f0df7baff59f3c63b65","status":"active","name":"AKT activation","description":"Signaling pathway whose impairment is associated with nutritional restriction.","types":["signaling pathway"],"aliases":["AKT signaling"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_206fbcd6a0fc5f0df7baff59f3c63b65"},{"public_id":"co_26e81865cd32e11bb762b3cf36932da2","status":"active","name":"somatotropic axis","description":"Endocrine axis involving GH and IGF-I that regulates body growth.","types":["endocrine axis"],"aliases":["GH/IGF-I axis"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_26e81865cd32e11bb762b3cf36932da2"},{"public_id":"co_3a5c2015194c99112eb6657eaf833480","status":"active","name":"underfed pups","description":"Mouse pups subjected to dietary restriction during early postnatal period.","types":["experimental group"],"aliases":["dietary-restricted pups"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_3a5c2015194c99112eb6657eaf833480"},{"public_id":"co_6940b6a1c72e73e2b1da9ce11bd30be1","status":"active","name":"dietary restriction","description":"Nutritional limitation during early postnatal period used to alter growth trajectory.","types":["experimental intervention"],"aliases":["underfeeding"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_6940b6a1c72e73e2b1da9ce11bd30be1"},{"public_id":"co_6f414430d6de4f52ef2196e9234ad7e4","status":"active","name":"GHRH neurons","description":"Growth Hormone Releasing Hormone neurons in the arcuate nucleus that control GH secretion.","types":["neuron type"],"aliases":["GHRH-expressing neurons"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_6f414430d6de4f52ef2196e9234ad7e4"},{"public_id":"co_7c716d4eb9bf0e3f2f4763680c60c477","status":"active","name":"in vitro arcuate explant cultures","description":"Cultured explants of the arcuate nucleus used to study axon elongation.","types":["experimental system"],"aliases":["arcuate explant cultures"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_7c716d4eb9bf0e3f2f4763680c60c477"},{"public_id":"co_9a5d2d481baf4e633a967f66766866b1","status":"active","name":"early postnatal period","description":"Lactation period in mice during which dietary restriction affects development.","types":["developmental stage"],"aliases":["perinatal period","lactation period"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_9a5d2d481baf4e633a967f66766866b1"},{"public_id":"co_a11a67d72184e6cf52ae875c6a2cd0ce","status":"active","name":"arcuate nucleus","description":"Hypothalamic region containing GHRH neurons and used for explant cultures.","types":["brain region"],"aliases":["arcuate nucleus of the hypothalamus"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_a11a67d72184e6cf52ae875c6a2cd0ce"},{"public_id":"co_ba30fe73362afd95b2d0cc3a92beeeaf","status":"active","name":"axon elongation","description":"Process of axon growth stimulated by IGF-I in GHRH neurons.","types":["cellular process"],"aliases":[],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_ba30fe73362afd95b2d0cc3a92beeeaf"},{"public_id":"co_cb69f18a9f5210ca0272d58f19e5058b","status":"active","name":"median eminence","description":"Hypothalamic structure innervated by GHRH axons.","types":["brain structure"],"aliases":[],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_cb69f18a9f5210ca0272d58f19e5058b"},{"public_id":"co_ec8541da46744b06d2916fbfa060fe06","status":"active","name":"normally fed pups","description":"Mouse pups fed ad libitum during early postnatal period.","types":["control group"],"aliases":["control pups"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_ec8541da46744b06d2916fbfa060fe06"},{"public_id":"co_f24c4a6ce62ac05405bd3eb00b42103c","status":"active","name":"IGF-1","description":"Insulin-like growth factor I that stimulates axon elongation of GHRH neurons.","types":["hormone"],"aliases":["IGF-I"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"}],"url":"https://sah.borca.ai/concepts/co_f24c4a6ce62ac05405bd3eb00b42103c"}],"external_ids":{"DOI":"10.1371/journal.pone.0170083","ArXiv":null,"PubMed":28076448,"PubMedCentral":"5226784","MAG":2572335422,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0170083&type=printable","landing_url":"https://www.semanticscholar.org/paper/49031ff01e594d8e11f709ea495b9d64543b0ceb","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":631638,"paper_uid":"b2e1bba4-2f89-408d-886f-2b5c7ed9a48c","canonical_identity":{"paper_id":631638,"paper_uid":"b2e1bba4-2f89-408d-886f-2b5c7ed9a48c","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/52820062"}