{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:42:39Z","timestamp":1791877359927,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["200646\/Z\/16\/Z"],"award-info":[{"award-number":["200646\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A key aim of Alzheimer disease research is to develop efficient therapies to prevent and\/or delay the irreversible progression of cognitive impairments. Early deficits in long\u2010term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR\u2010mediated long\u2010term depression (mGluR\u2010LTD) is affected. In this study, we have found that mGluR\u2010LTD is enhanced in the APP<jats:sub>swe<\/jats:sub>\/PS1dE9 mouse at 7 but returns to wild\u2010type levels at 13\u2009months of age. This transient over\u2010activation of mGluR signalling is coupled with impaired LTP and shifts the dynamic range of synapses towards depression. These alterations in synaptic plasticity are associated with an inability to utilize cues in a spatial learning task. The transient dysregulation of plasticity can be prevented by genetic deletion of the MAP kinase\u2010activated protein kinase 2 (MK2), a substrate of p38 MAPK, demonstrating that manipulating the mGluR\u2010p38 MAPK\u2010MK2 cascade at 7\u00a0months can prevent the shift in synapse dynamic range. Our work reveals the MK2 cascade as a potential pharmacological target to correct the over\u2010activation of mGluR signalling.<\/jats:p>","DOI":"10.1111\/acel.13717","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T14:43:48Z","timestamp":1663857828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The MK2 cascade mediates transient alteration in mGluR\u2010LTD and spatial learning in a murine model of Alzheimer's disease"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-8026","authenticated-orcid":false,"given":"Lucia","family":"Privitera","sequence":"first","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"},{"name":"School of Medicine, Ninewells Hospital University of Dundee  Dundee UK"},{"name":"Barts and the London School of Medicine Queen Mary University of London Malta Campus  Victoria Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen L.","family":"Hogg","sequence":"additional","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Lopes","sequence":"additional","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana B.","family":"Domingos","sequence":"additional","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-4652","authenticated-orcid":false,"given":"Matthias","family":"Gaestel","sequence":"additional","affiliation":[{"name":"Institute of Cell Biochemistry Hannover Medical University  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5487-0736","authenticated-orcid":false,"given":"J\u00fcrgen","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Wall","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Warwick  Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7434-1073","authenticated-orcid":false,"given":"Sonia A. L.","family":"Corr\u00eaa","sequence":"additional","affiliation":[{"name":"Bradford School of Pharmacy and Medical Sciences University of Bradford  Bradford UK"},{"name":"Faculty of Science and Engineering Manchester Metropolitan University  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-018-0364-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-79"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/80624"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.08.054"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/649079"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0144-15.2016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5701"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170457"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001735"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.04.077"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.095"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh019"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-019-00580-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.189"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/10061"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146357"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15007"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3486"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.12.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.01.022"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404670111"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.153122"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13294"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01316.2005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.025"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5575-08.2009"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.05.024"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.018"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.029"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00160"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1178"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720509790147070"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0325-8"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2017.03.023"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23981"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1115-1"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0288"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.036"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.012"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1633-03.2004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160763"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.05.014"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00088"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808247115"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.02.005"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13717","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13717","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13717","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:43:28Z","timestamp":1692607408000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/acel.13717"],"URL":"https:\/\/doi.org\/10.1111\/acel.13717","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]},"assertion":[{"value":"2022-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13717"}}