{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:36:07Z","timestamp":1789716967546,"version":"4.0.1"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Gerontology"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.exger.2018.02.005","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T12:39:47Z","timestamp":1517834387000},"page":"66-71","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B"],"prefix":"10.1016","volume":"104","author":[{"given":"Gabriel Keine","family":"Kuga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Rosetto","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Calais","family":"Gaspar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana Castelo Branco Ramos","family":"Nakandakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelino Sanchez Ramos","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Diego","family":"Botezelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Alexandre Curiacos de Almeida","family":"Leme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Jos\u00e9","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Pereira","family":"de Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennys Esper","family":"Cintra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Rochete","family":"Ropelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Rodrigo","family":"Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exger.2018.02.005_bb0005","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.nlm.2006.08.007","article-title":"mTOR signaling in the hippocampus is necessary for memory formation","volume":"87","author":"Bekinschtein","year":"2007","journal-title":"Neurobiol. Learn. Mem."},{"key":"10.1016\/j.exger.2018.02.005_bb0010","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1172\/JCI57256","article-title":"An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated A\u03b2 oligomers","volume":"122","author":"Bomfim","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.exger.2018.02.005_bb0015","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1210\/jcem-68-2-374","article-title":"Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies*","volume":"68","author":"Bonora","year":"1989","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.exger.2018.02.005_bb0020","doi-asserted-by":"crossref","DOI":"10.1038\/srep31106","article-title":"Strength training prevents hyperinsulinemia, insulin resistance, and inflammation independent of weight loss in fructose-fed animals","volume":"6","author":"Botezelli","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exger.2018.02.005_bb0025","doi-asserted-by":"crossref","first-page":"E649","DOI":"10.1152\/ajpendo.00272.2013","article-title":"Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats","volume":"305","author":"Chiarreotto-Ropelle","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.exger.2018.02.005_bb0030","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.jalz.2013.12.004","article-title":"How does brain insulin resistance develop in Alzheimer's disease?","volume":"10","author":"De Felice","year":"2014","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.exger.2018.02.005_bb0035","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/193229680800200619","article-title":"Alzheimer's disease is type 3 diabetes-evidence reviewed","volume":"2","author":"de la Monte","year":"2008","journal-title":"J. Diabetes Sci. Technol."},{"key":"10.1016\/j.exger.2018.02.005_bb0040","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/JAD-2006-10113","article-title":"Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer's disease","volume":"10","author":"de la Monte","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.exger.2018.02.005_bb0045","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-4933-10-8","article-title":"Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats","volume":"10","author":"de Moura","year":"2013","journal-title":"Immun. Ageing"},{"key":"10.1016\/j.exger.2018.02.005_bb0050","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/hipo.22261","article-title":"Spatial memory in sedentary and trained diabetic rats: molecular mechanisms","volume":"24","author":"Diegues","year":"2014","journal-title":"Hippocampus"},{"key":"10.1016\/j.exger.2018.02.005_bb0055","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pneurobio.2014.02.004","article-title":"What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus","volume":"117","author":"Fjell","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.exger.2018.02.005_bb0060","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.exger.2018.02.005_bb0065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0041536","article-title":"Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning","volume":"7","author":"Fuentes","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.exger.2018.02.005_bb0070","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1037\/bne0000080","article-title":"Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze","volume":"129","author":"Gallagher","year":"2015","journal-title":"Behav. Neurosci."},{"key":"10.1016\/j.exger.2018.02.005_bb0075","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1742-2094-5-51","article-title":"Inflammaging as a prodrome to Alzheimer's disease","volume":"5","author":"Giunta","year":"2008","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.exger.2018.02.005_bb0080","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1474-9726.2011.00786.x","article-title":"Essential role of protein tyrosine phosphatase 1B in obesity-induced inflammation and peripheral insulin resistance during aging","volume":"11","author":"Gonz\u00e1lez-Rodr\u00edguez","year":"2012","journal-title":"Aging Cell"},{"key":"10.1016\/j.exger.2018.02.005_bb0085","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.2337\/db15-0596","article-title":"Hippocampal insulin resistance impairs spatial learning and synaptic plasticity","volume":"64","author":"Grillo","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.exger.2018.02.005_bb0090","doi-asserted-by":"crossref","first-page":"16755","DOI":"10.1523\/JNEUROSCI.4521-10.2010","article-title":"Reimagining Alzheimer's disease\u2014an age-based hypothesis","volume":"30","author":"Herrup","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.exger.2018.02.005_bb0095","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1212\/WNL.54.11.2072","article-title":"Age-specific incidence rates of Alzheimer's disease: the Baltimore longitudinal study of aging","volume":"54","author":"Kawas","year":"2000","journal-title":"Neurology"},{"key":"10.1016\/j.exger.2018.02.005_bb0100","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3233\/JAD-2006-9102","article-title":"Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease","volume":"9","author":"Lester-Coll","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.exger.2018.02.005_bb0105","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1007\/s10072-014-1784-7","article-title":"Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats","volume":"35","author":"Li","year":"2014","journal-title":"Neurol. Sci."},{"key":"10.1016\/j.exger.2018.02.005_bb0110","article-title":"Endoplasmic reticulum stress impairs insulin receptor signaling in the brains of obese rats","volume":"10","author":"Liang","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.exger.2018.02.005_bb0115","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cmet.2013.11.002","article-title":"TNF-\u03b1 mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer's \u03b2-amyloid oligomers in mice and monkeys","volume":"18","author":"Lourenco","year":"2013","journal-title":"Cell Metab."},{"key":"10.1016\/j.exger.2018.02.005_bb0120","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1210\/en.2006-0672","article-title":"Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin resistance with age","volume":"148","author":"Morrison","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.exger.2018.02.005_bb0125","article-title":"Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice","author":"Mu\u00f1oz","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"10.1016\/j.exger.2018.02.005_bb0130","doi-asserted-by":"crossref","first-page":"31682","DOI":"10.1074\/jbc.M114.603621","article-title":"Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling","volume":"289","author":"Ozek","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.exger.2018.02.005_bb0135","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbr.2012.10.060","article-title":"Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory","volume":"240","author":"Palmeri","year":"2013","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.exger.2018.02.005_bb0140","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.bcp.2014.01.011","article-title":"Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines","volume":"88","author":"Puzzo","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.exger.2018.02.005_bb0145","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.neurobiolaging.2005.01.004","article-title":"Insulin, insulin-degrading enzyme and amyloid-\u03b2 peptide in Alzheimer's disease: review and hypothesis","volume":"27","author":"Qiu","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.exger.2018.02.005_bb0150","doi-asserted-by":"crossref","first-page":"32730","DOI":"10.1074\/jbc.273.49.32730","article-title":"Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation","volume":"273","author":"Qiu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.exger.2018.02.005_bb0155","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1113\/jphysiol.2006.120006","article-title":"Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation","volume":"577","author":"Ropelle","year":"2006","journal-title":"J. Physiol."},{"key":"10.1016\/j.exger.2018.02.005_bb0160","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1073\/pnas.0308724101","article-title":"Role for neuronal insulin resistance in neurodegenerative diseases","volume":"101","author":"Schubert","year":"2004","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.exger.2018.02.005_bb0165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0006007","article-title":"BDNF activates mTOR to regulate GluR1 expression required for memory formation","volume":"4","author":"Slipczuk","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.exger.2018.02.005_bb0170","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1039\/c0mb00302f","article-title":"Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function","volume":"7","author":"Takeda","year":"2011","journal-title":"Mol. BioSyst."},{"key":"10.1016\/j.exger.2018.02.005_bb0175","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2017.00007","article-title":"Protein tyrosine phosphatase 1B (PTP1B): a potential target for Alzheimer's therapy?","volume":"9","author":"Vieira","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.exger.2018.02.005_bb0180","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bbr.2014.02.005","article-title":"mTOR and autophagy in normal brain aging and caloric restriction ameliorating age-related cognition deficits","volume":"264","author":"Yang","year":"2014","journal-title":"Behav. Brain Res."}],"container-title":["Experimental Gerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0531556517308665?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0531556517308665?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,24]],"date-time":"2018-08-24T05:41:13Z","timestamp":1535089273000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0531556517308665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":36,"alternative-id":["S0531556517308665"],"URL":"https:\/\/doi.org\/10.1016\/j.exger.2018.02.005","relation":{},"ISSN":["0531-5565"],"issn-type":[{"value":"0531-5565","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B","name":"articletitle","label":"Article Title"},{"value":"Experimental Gerontology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exger.2018.02.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}