{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:26:45Z","timestamp":1790836005584,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010897","name":"Newton Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The nucleoside guanosine is an endogenous neuromodulator associated with neuroprotection. The roles of guanosine during aging are still not fully elucidated. Guanosine modulates SUMOylation in neurons and astrocytes in vitro, but it is not known whether guanosine can modulate SUMOylation in vivo and improve cognitive functions during aging. SUMOylation is a post\u2010translational protein modification with potential neuroprotective roles. In this follow\u2010up study, we investigated whether guanosine could modulate SUMOylation in vivo and behavior in young and aged mice. Young (3\u2010month\u2010old) and aged (24\u2010month\u2010old) C57BL\/6 mice were treated with guanosine (8\u2009mg\/kg intraperitoneal) daily for 14\u2009days. Starting on day 8 of treatment, the following behavioral tests were performed: open field, novel object location, Y\u2010maze, sucrose splash test, and tail suspension test. Treatment with guanosine did not change the locomotor activity of young or aged mice in the open\u2010field test. Treatment with guanosine improved short\u2010term memory only for young mice but did not change the working memory of either young or aged mice, as evaluated using object recognition and the Y\u2010maze tests, respectively. Depressive\u2010like behaviors, such as impaired grooming evaluated through the splash test, did not change in either young or aged mice. However, young mice treated with guanosine increased their immobility time in the tail suspension test, suggesting an effect on behavioral coping strategies. Global SUMO1\u2010ylation was significantly increased in the hippocampus of young and aged mice after 14\u2009days of treatment with guanosine, whereas no changes were detected in the cerebral cortex of either young or aged mice. Our findings demonstrate that guanosine also targets hippocampal SUMOylation in vivo, thereby contributing to a deeper understanding of its mechanisms of action. This highlights the involvement of SUMOylation in guanosine's modulatory and neuroprotective effects.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15920-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15920","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T06:44:38Z","timestamp":1690353878000},"page":"1503-1513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Guanosine increases global <scp>SUMO1<\/scp>\u2010ylation in the hippocampus of young and aged mice and improves the short\u2010term memory of young mice"],"prefix":"10.1111","volume":"168","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-5765","authenticated-orcid":false,"given":"Camila A.","family":"Zanella","sequence":"first","affiliation":[{"name":"Pharmacology Department, Pharmacology Postgraduate Program Biological Sciences Center (CCB) Federal University of Santa Catarina (UFSC)  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1747-4793","authenticated-orcid":false,"given":"Naiani","family":"Marques","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Biochemistry Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5914-1439","authenticated-orcid":false,"given":"Stella","family":"Junqueira","sequence":"additional","affiliation":[{"name":"Neuroscience Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-6463","authenticated-orcid":false,"given":"Rui D.","family":"Prediger","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Pharmacology Postgraduate Program Biological Sciences Center (CCB) Federal University of Santa Catarina (UFSC)  Florian\u00f3polis Brazil"},{"name":"Neuroscience Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-6150","authenticated-orcid":false,"given":"Carla I.","family":"Tasca","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Biochemistry Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"},{"name":"Neuroscience Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-480X","authenticated-orcid":false,"given":"Helena I.","family":"Cimarosti","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Pharmacology Postgraduate Program Biological Sciences Center (CCB) Federal University of Santa Catarina (UFSC)  Florian\u00f3polis Brazil"},{"name":"Neuroscience Postgraduate Program, CCB, UFSC  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20102094\u20106\u201012"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JALZ.2018.02.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-7002-2_12"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.06.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13172"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1747\u20101028\u20101\u201013"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.09.010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12121207"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001457"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.05.021"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302\u2010019\u201009679\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.05.033"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00158"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13008\u2010015\u20100010\u20101"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2009.06692.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.01.004"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2009.01.009"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.04.002"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2293"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010014\u20108978\u20100"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.4155\/fso.15.38"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.03.012"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.02.004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2014"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100101\u2010y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14001"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3505"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00090"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8994-2_10"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2016.0208"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010016\u20100082\u20101"},{"issue":"1630","key":"e_1_2_10_34_1","first-page":"1","article-title":"Adenosine A1\u2010A2A receptor\u2010receptor interaction: Contribution to guanosine\u2010mediated effects","volume":"8","author":"Lanznaster D.","year":"2019","journal-title":"Cell"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26509"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.112014"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.653146"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201025150\u2010z"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22681"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2011.11.009"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640\u2010015\u20109540\u20101"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/948241"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wnr.0000123386.87650.ab"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010020\u201001977\u20104"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2017.01.002"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2019.09.012"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114216"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2010.02.036"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.422607"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6252"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.01.004"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.01.003"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.07.004"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150200032"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3791\/52434"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874609809666160211124947"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302\u2010016\u20109533\u20104"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12760"},{"issue":"3","key":"e_1_2_10_60_1","first-page":"673","article-title":"Guanosine promotes proliferation of neural stem cells through cAMP\u2010CREB pathway","volume":"27","author":"Su C.","year":"2013","journal-title":"Journal of Biological Regulators and Homeostatic Agents"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.09003"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.10.041"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00376"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-1047(84)90555-7"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302\u2010016\u20109534\u20103"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20327"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0831s69"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100158"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2010.04.002"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.01.012"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.027"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302\u2010020\u201009723\u20100"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15920","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:56:40Z","timestamp":1722333400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,25]]},"references-count":71,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/jnc.15920"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15920","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,25]]},"assertion":[{"value":"2023-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}