{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:44:04Z","timestamp":1785260644936,"version":"3.55.0"},"reference-count":71,"publisher":"Life Science Alliance, LLC","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"crossref","award":["UKDRI-2001"],"award-info":[{"award-number":["UKDRI-2001"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MRC MC_U132692719"],"award-info":[{"award-number":["MRC MC_U132692719"]}]},{"name":"European Research Council","award":["647479"],"award-info":[{"award-number":["647479"]}]},{"DOI":"10.13039\/100013278","name":"JPND","doi-asserted-by":"crossref","award":["MR\/R024820\/1"],"award-info":[{"award-number":["MR\/R024820\/1"]}],"id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CoEN","award":["MR\/S00503X\/1"],"award-info":[{"award-number":["MR\/S00503X\/1"]}]},{"name":"Wellcome Trust Collaborative Award","award":["201487\/Z\/16\/Z"],"award-info":[{"award-number":["201487\/Z\/16\/Z"]}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Increasing levels of the cold-shock protein, RNA-binding motif 3 (RBM3), either through cooling or by ectopic over-expression, prevents synapse and neuronal loss in mouse models of neurodegeneration. To exploit this process therapeutically requires an understanding of mechanisms controlling cold-induced RBM3 expression. Here, we show that cooling increases RBM3 through activation of TrkB via PLC\u03b31 and pCREB signaling. RBM3, in turn, has a hitherto unrecognized negative feedback on TrkB-induced ERK activation through induction of its specific phosphatase, DUSP6. Thus, RBM3 mediates structural plasticity through a distinct, non-canonical activation of TrkB signaling, which is abolished in RBM3-null neurons. Both genetic reduction and pharmacological antagonism of TrkB and its downstream mediators abrogate cooling-induced RBM3 induction and prevent structural plasticity, whereas TrkB inhibition similarly prevents RBM3 induction and the neuroprotective effects of cooling in prion-diseased mice. Conversely, TrkB agonism induces RBM3 without cooling, preventing synapse loss and neurodegeneration. TrkB signaling is, therefore, necessary for the induction of RBM3 and related neuroprotective effects and provides a target by which RBM3-mediated synapse-regenerative therapies in neurodegenerative disorders can be used therapeutically without the need for inducing hypothermia.<\/jats:p>","DOI":"10.26508\/lsa.202000884","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T15:25:25Z","timestamp":1612884325000},"page":"e202000884","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection"],"prefix":"10.26508","volume":"4","author":[{"given":"Diego","family":"Peretti","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L","family":"Smith","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Verity","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit at the University of Cambridge, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Humoud","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lis","family":"de Weerd","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P","family":"Swinden","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Hayes","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-1191","authenticated-orcid":true,"given":"Giovanna R","family":"Mallucci","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, Island Research Building, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"2021020907250702000_4.4.e202000884.1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1561"},{"key":"2021020907250702000_4.4.e202000884.2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.67804"},{"key":"2021020907250702000_4.4.e202000884.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316335111"},{"key":"2021020907250702000_4.4.e202000884.4","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a015818"},{"key":"2021020907250702000_4.4.e202000884.5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601087"},{"key":"2021020907250702000_4.4.e202000884.6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx198"},{"key":"2021020907250702000_4.4.e202000884.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.01.047"},{"key":"2021020907250702000_4.4.e202000884.8","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.099"},{"key":"2021020907250702000_4.4.e202000884.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2010.02.001"},{"key":"2021020907250702000_4.4.e202000884.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.10.034"},{"key":"2021020907250702000_4.4.e202000884.11","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695810"},{"key":"2021020907250702000_4.4.e202000884.12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43992"},{"key":"2021020907250702000_4.4.e202000884.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912973107"},{"key":"2021020907250702000_4.4.e202000884.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115907108"},{"key":"2021020907250702000_4.4.e202000884.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718683115"},{"key":"2021020907250702000_4.4.e202000884.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.04.010"},{"key":"2021020907250702000_4.4.e202000884.17","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7059"},{"key":"2021020907250702000_4.4.e202000884.18","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.191"},{"key":"2021020907250702000_4.4.e202000884.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409764102"},{"key":"2021020907250702000_4.4.e202000884.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.05.043"},{"key":"2021020907250702000_4.4.e202000884.21","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.49"},{"key":"2021020907250702000_4.4.e202000884.22","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx074"},{"key":"2021020907250702000_4.4.e202000884.23","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2019.00024"},{"key":"2021020907250702000_4.4.e202000884.24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161629"},{"key":"2021020907250702000_4.4.e202000884.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.08.012"},{"key":"2021020907250702000_4.4.e202000884.26","doi-asserted-by":"publisher","DOI":"10.1159\/000493637"},{"key":"2021020907250702000_4.4.e202000884.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913572107"},{"key":"2021020907250702000_4.4.e202000884.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.001"},{"key":"2021020907250702000_4.4.e202000884.29","doi-asserted-by":"publisher","DOI":"10.1177\/1941874413519802"},{"key":"2021020907250702000_4.4.e202000884.30","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20141014"},{"key":"2021020907250702000_4.4.e202000884.31","doi-asserted-by":"publisher","DOI":"10.1261\/rna.054411.115"},{"key":"2021020907250702000_4.4.e202000884.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.01.006"},{"key":"2021020907250702000_4.4.e202000884.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089680"},{"key":"2021020907250702000_4.4.e202000884.34","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3237"},{"key":"2021020907250702000_4.4.e202000884.35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562561"},{"key":"2021020907250702000_4.4.e202000884.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.10.033"},{"key":"2021020907250702000_4.4.e202000884.37","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5709"},{"key":"2021020907250702000_4.4.e202000884.38","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.3.202"},{"key":"2021020907250702000_4.4.e202000884.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090187"},{"key":"2021020907250702000_4.4.e202000884.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.005"},{"key":"2021020907250702000_4.4.e202000884.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.06.038"},{"key":"2021020907250702000_4.4.e202000884.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00942-X"},{"key":"2021020907250702000_4.4.e202000884.43","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2738"},{"key":"2021020907250702000_4.4.e202000884.44","doi-asserted-by":"publisher","DOI":"10.1038\/nature11058"},{"key":"2021020907250702000_4.4.e202000884.45","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9193534"},{"key":"2021020907250702000_4.4.e202000884.46","doi-asserted-by":"publisher","DOI":"10.1038\/nature14142"},{"key":"2021020907250702000_4.4.e202000884.47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020329"},{"key":"2021020907250702000_4.4.e202000884.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25668-2"},{"key":"2021020907250702000_4.4.e202000884.49","doi-asserted-by":"publisher","DOI":"10.1038\/35049004"},{"key":"2021020907250702000_4.4.e202000884.50","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90337-2"},{"key":"2021020907250702000_4.4.e202000884.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.07.059"},{"key":"2021020907250702000_4.4.e202000884.52","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0740125.x"},{"key":"2021020907250702000_4.4.e202000884.53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210041"},{"key":"2021020907250702000_4.4.e202000884.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80563-2"},{"key":"2021020907250702000_4.4.e202000884.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.058"},{"key":"2021020907250702000_4.4.e202000884.56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.33.20175"},{"key":"2021020907250702000_4.4.e202000884.57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0921-20.2020"},{"key":"2021020907250702000_4.4.e202000884.58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04521.x"},{"key":"2021020907250702000_4.4.e202000884.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.12.014"},{"key":"2021020907250702000_4.4.e202000884.60","doi-asserted-by":"publisher","DOI":"10.1101\/lm.049395.119"},{"key":"2021020907250702000_4.4.e202000884.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.07.007"},{"key":"2021020907250702000_4.4.e202000884.62","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2874-06.2006"},{"key":"2021020907250702000_4.4.e202000884.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4385-06.2007"},{"key":"2021020907250702000_4.4.e202000884.64","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201407065"},{"key":"2021020907250702000_4.4.e202000884.65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802759105"},{"key":"2021020907250702000_4.4.e202000884.66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089680"},{"key":"2021020907250702000_4.4.e202000884.67","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201801143"},{"key":"2021020907250702000_4.4.e202000884.68","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14588"},{"key":"2021020907250702000_4.4.e202000884.69","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3174"},{"key":"2021020907250702000_4.4.e202000884.70","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2014.00006"},{"key":"2021020907250702000_4.4.e202000884.71","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.243"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202000884","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:02:34Z","timestamp":1704895354000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202000884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,9]]},"references-count":71,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2,9]]},"published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.26508\/lsa.202000884"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202000884","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,9]]}}}