{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:43:07Z","timestamp":1793911387381,"version":"4.8.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Adiponectin is an adipokine that regulates apoptosis, glucose and lipid metabolism, and insulin sensitivity in metabolic diseases. As recent studies have associated changes in adipokines and other metabolites in the central nervous system with a risk for Alzheimer\u2019s disease (AD), we investigated the effects of adiponectin treatment on hippocampal cells in the 5XFAD mouse model of AD and neuronal SH-SY5Y cells under amyloid beta toxicity. Adiponectin treatment reduced levels of cleaved caspase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) apoptosis signalling and decreased glycogen synthase kinase 3 beta (GSK3\u03b2) activation. Moreover, adiponectin treatment triggered long-term potentiation in the hippocampi of 5XFAD mice, which was associated with reduced expression of\n                    <jats:italic>N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate and its receptor as well as surface expression of the \u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that adiponectin inhibits neuronal apoptosis and inflammatory mechanisms and promotes hippocampal long-term potentiation. Thus, adiponectin exhibits beneficial effect on hippocampal synaptic plasticity in Alzheimer\u2019s disease mouse model.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-45509-0","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T06:03:04Z","timestamp":1561010584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Adiponectin improves long-term potentiation in the 5XFAD mouse brain"],"prefix":"10.1038","volume":"9","author":[{"given":"Ming","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihoon","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9165-8507","authenticated-orcid":false,"given":"Juhyun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"45509_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.beem.2013.06.006","volume":"28","author":"KK Cheng","year":"2014","unstructured":"Cheng, K. K., Lam, K. S., Wang, B. & Xu, A. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin. Best practice & research. Clinical endocrinology & metabolism 28, 3\u201313, https:\/\/doi.org\/10.1016\/j.beem.2013.06.006 (2014).","journal-title":"Best practice & research. Clinical endocrinology & metabolism"},{"key":"45509_CR2","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1172\/JCI14120","volume":"108","author":"TP Combs","year":"2001","unstructured":"Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E. & Rossetti, L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. The Journal of clinical investigation 108, 1875\u20131881, https:\/\/doi.org\/10.1172\/JCI14120 (2001).","journal-title":"The Journal of clinical investigation"},{"key":"45509_CR3","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nm1557","volume":"13","author":"T Yamauchi","year":"2007","unstructured":"Yamauchi, T. et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nature medicine 13, 332\u2013339, https:\/\/doi.org\/10.1038\/nm1557 (2007).","journal-title":"Nature medicine"},{"key":"45509_CR4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s11011-015-9739-0","volume":"31","author":"M Gorska-Ciebiada","year":"2016","unstructured":"Gorska-Ciebiada, M., Saryusz-Wolska, M., Borkowska, A., Ciebiada, M. & Loba, J. Adiponectin, leptin and IL-1 beta in elderly diabetic patients with mild cognitive impairment. Metabolic brain disease 31, 257\u2013266, https:\/\/doi.org\/10.1007\/s11011-015-9739-0 (2016).","journal-title":"Metabolic brain disease"},{"key":"45509_CR5","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.3233\/JAD-151116","volume":"52","author":"M Waragai","year":"2016","unstructured":"Waragai, M. et al. Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer\u2019s Disease. Journal of Alzheimer\u2019s disease: JAD 52, 1453\u20131459, https:\/\/doi.org\/10.3233\/JAD-151116 (2016).","journal-title":"Journal of Alzheimer\u2019s disease: JAD"},{"key":"45509_CR6","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.jdiacomp.2015.12.001","volume":"30","author":"N Garcia-Casares","year":"2016","unstructured":"Garcia-Casares, N. et al. Alzheimer\u2019s like brain changes correlate with low adiponectin plasma levels in type 2 diabetic patients. Journal of diabetes and its complications 30, 281\u2013286, https:\/\/doi.org\/10.1016\/j.jdiacomp.2015.12.001 (2016).","journal-title":"Journal of diabetes and its complications"},{"key":"45509_CR7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s12017-012-8201-2","volume":"15","author":"AL Teixeira","year":"2013","unstructured":"Teixeira, A. L. et al. Decreased levels of circulating adiponectin in mild cognitive impairment and Alzheimer\u2019s disease. Neuromolecular medicine 15, 115\u2013121, https:\/\/doi.org\/10.1007\/s12017-012-8201-2 (2013).","journal-title":"Neuromolecular medicine"},{"key":"45509_CR8","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1179\/1743132812Y.0000000127","volume":"35","author":"T Kurata","year":"2013","unstructured":"Kurata, T. et al. Atorvastatin and pitavastatin reduce oxidative stress and improve IR\/LDL-R signals in Alzheimer\u2019s disease. Neurological research 35, 193\u2013205, https:\/\/doi.org\/10.1179\/1743132812Y.0000000127 (2013).","journal-title":"Neurological research"},{"key":"45509_CR9","doi-asserted-by":"publisher","first-page":"9695","DOI":"10.1523\/JNEUROSCI.2014-06.2006","volume":"26","author":"M Fry","year":"2006","unstructured":"Fry, M. et al. Area postrema neurons are modulated by the adipocyte hormone adiponectin. The Journal of neuroscience: the official journal of the Society for Neuroscience 26, 9695\u20139702, https:\/\/doi.org\/10.1523\/JNEUROSCI.2014-06.2006 (2006).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"45509_CR10","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/90984","volume":"7","author":"T Yamauchi","year":"2001","unstructured":"Yamauchi, T. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature medicine 7, 941\u2013946, https:\/\/doi.org\/10.1038\/90984 (2001).","journal-title":"Nature medicine"},{"key":"45509_CR11","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nrn3200","volume":"13","author":"JH Morrison","year":"2012","unstructured":"Morrison, J. H. & Baxter, M. G. The ageing cortical synapse: hallmarks and implications for cognitive decline. Nature reviews. Neuroscience 13, 240\u2013250, https:\/\/doi.org\/10.1038\/nrn3200 (2012).","journal-title":"Nature reviews. Neuroscience"},{"key":"45509_CR12","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1152\/physrev.00014.2003","volume":"84","author":"MA Lynch","year":"2004","unstructured":"Lynch, M. A. Long-term potentiation and memory. Physiological reviews 84, 87\u2013136, https:\/\/doi.org\/10.1152\/physrev.00014.2003 (2004).","journal-title":"Physiological reviews"},{"key":"45509_CR13","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.neuron.2013.10.025","volume":"80","author":"RL Huganir","year":"2013","unstructured":"Huganir, R. L. & Nicoll, R. A. AMPARs and synaptic plasticity: the last 25 years. Neuron 80, 704\u2013717, https:\/\/doi.org\/10.1016\/j.neuron.2013.10.025 (2013).","journal-title":"Neuron"},{"key":"45509_CR14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nature13294","volume":"511","author":"S Nabavi","year":"2014","unstructured":"Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348\u2013352, https:\/\/doi.org\/10.1038\/nature13294 (2014).","journal-title":"Nature"},{"issue":"5","key":"45509_CR15","doi-asserted-by":"publisher","first-page":"e21964","DOI":"10.1002\/syn.21964","volume":"71","author":"Filippo Weisz","year":"2017","unstructured":"Weisz, F. et al. The role of adiponectin receptors in the regulation of synaptic transmission in the hippocampus. Synapse 71, https:\/\/doi.org\/10.1002\/syn.21964 (2017).","journal-title":"Synapse"},{"key":"45509_CR16","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.neulet.2017.10.042","volume":"662","author":"F Pousti","year":"2018","unstructured":"Pousti, F., Ahmadi, R., Mirahmadi, F., Hosseinmardi, N. & Rohampour, K. Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus. Neuroscience letters 662, 227\u2013232, https:\/\/doi.org\/10.1016\/j.neulet.2017.10.042 (2018).","journal-title":"Neuroscience letters"},{"key":"45509_CR17","doi-asserted-by":"publisher","first-page":"102","DOI":"10.5152\/balkanmedj.2015.15084","volume":"33","author":"M Ghasemi","year":"2016","unstructured":"Ghasemi, M. et al. Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats. Balkan medical journal 33, 102\u2013107, https:\/\/doi.org\/10.5152\/balkanmedj.2015.15084 (2016).","journal-title":"Balkan medical journal"},{"key":"45509_CR18","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","volume":"26","author":"H Oakley","year":"2006","unstructured":"Oakley, H. et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation. The Journal of neuroscience: the official journal of the Society for Neuroscience 26, 10129\u201310140, https:\/\/doi.org\/10.1523\/JNEUROSCI.1202-06.2006 (2006).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"45509_CR19","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.3109\/09553002.2013.817701","volume":"89","author":"H Wang","year":"2013","unstructured":"Wang, H. et al. Impairment of long-term potentiation induction is essential for the disruption of spatial memory after microwave exposure. International journal of radiation biology 89, 1100\u20131107, https:\/\/doi.org\/10.3109\/09553002.2013.817701 (2013).","journal-title":"International journal of radiation biology"},{"key":"45509_CR20","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1210\/jc.2006-1841","volume":"92","author":"K Kos","year":"2007","unstructured":"Kos, K. et al. Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus. The Journal of clinical endocrinology and metabolism 92, 1129\u20131136, https:\/\/doi.org\/10.1210\/jc.2006-1841 (2007).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"45509_CR21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1385\/NMM:6:1:053","volume":"6","author":"CW Xie","year":"2004","unstructured":"Xie, C. W. Calcium-regulated signaling pathways: role in amyloid beta-induced synaptic dysfunction. Neuromolecular medicine 6, 53\u201364, https:\/\/doi.org\/10.1385\/NMM:6:1:053 (2004).","journal-title":"Neuromolecular medicine"},{"key":"45509_CR22","doi-asserted-by":"publisher","first-page":"7821","DOI":"10.1523\/JNEUROSCI.1697-04.2004","volume":"24","author":"PV Massey","year":"2004","unstructured":"Massey, P. V. et al. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. The Journal of neuroscience: the official journal of the Society for Neuroscience 24, 7821\u20137828, https:\/\/doi.org\/10.1523\/JNEUROSCI.1697-04.2004 (2004).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"45509_CR23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrn2055","volume":"8","author":"VA Derkach","year":"2007","unstructured":"Derkach, V. A., Oh, M. C., Guire, E. S. & Soderling, T. R. Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nature reviews. Neuroscience 8, 101\u2013113, https:\/\/doi.org\/10.1038\/nrn2055 (2007).","journal-title":"Nature reviews. Neuroscience"},{"key":"45509_CR24","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nn.2785","volume":"14","author":"J Jo","year":"2011","unstructured":"Jo, J. et al. Abeta(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3beta. Nat Neurosci 14, 545\u2013547, https:\/\/doi.org\/10.1038\/nn.2785 (2011).","journal-title":"Nat Neurosci"},{"key":"45509_CR25","doi-asserted-by":"publisher","first-page":"25457","DOI":"10.1074\/jbc.M603469200","volume":"281","author":"F Plattner","year":"2006","unstructured":"Plattner, F., Angelo, M. & Giese, K. P. The roles of cyclin-dependent kinase 5 and glycogen synthase kinase 3 in tau hyperphosphorylation. The Journal of biological chemistry 281, 25457\u201325465, https:\/\/doi.org\/10.1074\/jbc.M603469200 (2006).","journal-title":"The Journal of biological chemistry"},{"key":"45509_CR26","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.neuron.2007.01.029","volume":"53","author":"S Peineau","year":"2007","unstructured":"Peineau, S. et al. LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53, 703\u2013717, https:\/\/doi.org\/10.1016\/j.neuron.2007.01.029 (2007).","journal-title":"Neuron"},{"key":"45509_CR27","doi-asserted-by":"publisher","first-page":"11462","DOI":"10.1158\/0008-5472.CAN-06-1969","volume":"66","author":"Y Wang","year":"2006","unstructured":"Wang, Y. et al. Adiponectin modulates the glycogen synthase kinase-3beta\/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer research 66, 11462\u201311470, https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-1969 (2006).","journal-title":"Cancer research"},{"key":"45509_CR28","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/s12035-013-8428-4","volume":"48","author":"R Niranjan","year":"2013","unstructured":"Niranjan, R. Molecular basis of etiological implications in Alzheimer\u2019s disease: focus on neuroinflammation. Molecular neurobiology 48, 412\u2013428, https:\/\/doi.org\/10.1007\/s12035-013-8428-4 (2013).","journal-title":"Molecular neurobiology"},{"key":"45509_CR29","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3233\/JAD-2010-1219","volume":"19","author":"EG McGeer","year":"2010","unstructured":"McGeer, E. G. & McGeer, P. L. Neuroinflammation in Alzheimer\u2019s disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis 19, 355\u2013361, https:\/\/doi.org\/10.3233\/JAD-2010-1219 (2010).","journal-title":"J Alzheimers Dis"},{"key":"45509_CR30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3132\/dvdr.2008.020","volume":"5","author":"A Tomizawa","year":"2008","unstructured":"Tomizawa, A., Hattori, Y., Kasai, K. & Nakano, Y. Adiponectin induces NF-kappaB activation that leads to suppression of cytokine-induced NF-kappaB activation in vascular endothelial cells: globular adiponectin vs. high molecular weight adiponectin. Diabetes & vascular disease research 5, 123\u2013127, https:\/\/doi.org\/10.3132\/dvdr.2008.020 (2008).","journal-title":"Diabetes & vascular disease research"},{"key":"45509_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-6-47","volume":"6","author":"K An","year":"2013","unstructured":"An, K. et al. Exosomes neutralize synaptic-plasticity-disrupting activity of Abeta assemblies in vivo. Molecular brain 6, 47, https:\/\/doi.org\/10.1186\/1756-6606-6-47 (2013).","journal-title":"Molecular brain"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45509-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45509-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45509-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T05:36:09Z","timestamp":1671255369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45509-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45509"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45509-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,20]]},"assertion":[{"value":"16 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8918"}}