{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:41:44Z","timestamp":1788633704674,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2019\u2010109033RB\u2010100"],"award-info":[{"award-number":["PID2019\u2010109033RB\u2010100"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2022\u2010137932NB\u2010I00"],"award-info":[{"award-number":["PID2022\u2010137932NB\u2010I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010784","name":"Banco Santander","doi-asserted-by":"publisher","award":["PR41\/17\u201020979"],"award-info":[{"award-number":["PR41\/17\u201020979"]}],"id":[{"id":"10.13039\/100010784","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The exact causes of major depressive disorder (MDD) are still debated, but its connection with inflammatory diseases and stress is well established. Emerging evidence suggests a potential link between periodontitis (gum disease) and MDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Periodontitis (P) was induced in rats through oral rinses with the pathogenic bacteria\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      <\/jats:styled-content>\n                      for 12\u2009weeks, followed by 3\u2009weeks of chronic mild stress (CMS) to induce depressive\u2010like behavior. Four experimental groups were established: periodontitis with CMS (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009+\u2009CMS+), periodontitis without CMS (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009+\u2009CMS\u2010), CMS without periodontitis (P\u2010CMS+), and control (P\u2010CMS\u2010). Inflammatory and synaptic plasticity\u2010related mediators were quantified in hippocampal samples. The number, morphology, and inflammatory phenotype of microglia were also evaluated by ultrastructural and fractal analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P<\/jats:italic>\n                      \u2009+\u2009CMS+ animals compared with controls showed: (1) increased protein expression of TLR\u20104, phospho(p)\u2010nuclear factor kappa B (p\u2010NF\u03baB)\/NF\u03baB ratio, and inducible nitric oxide synthase (iNOS); (2) decreased microglial number, shorter branch length, reduced complexity, and increased expression of iNOS; (3) decreased protein levels of BDNF and synaptophysin, and lower ratios of p\u2010protein kinase B (p\u2010Akt)\/Akt and p\u2010mammalian target of rapamycin (p\u2010mTOR)\/mTOR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Alterations in neuroinflammation and neuroplasticity in the hippocampus may contribute to the comorbidity between periodontitis and MDD, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70669","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T04:33:04Z","timestamp":1764649984000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Alterations in Neuroinflammation, Microglia and Neuroplasticity in the Rat Hippocampus in a Combined Model of Periodontitis and Depression"],"prefix":"10.1111","volume":"31","author":[{"given":"Javier","family":"Robledo\u2010Monta\u00f1a","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research)  Madrid Spain"},{"name":"Biomedical Network Research Center of Mental Health (CIBERSAM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mart\u00edn\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research)  Madrid Spain"},{"name":"Biomedical Network Research Center of Mental Health (CIBERSAM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2193-9991","authenticated-orcid":false,"given":"Javier","family":"Cuenca\u2010Ortega","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research)  Madrid Spain"},{"name":"Biomedical Network Research Center of Mental Health (CIBERSAM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3376-5232","authenticated-orcid":false,"given":"Leire","family":"Virto","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Anatomy and Embryology, Faculty of Optics and Optometry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9837-5393","authenticated-orcid":false,"given":"Nagore","family":"Ambrosio","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-8529","authenticated-orcid":false,"given":"Eduardo","family":"Montero","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Herrera","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-5755","authenticated-orcid":false,"given":"Mariano","family":"Sanz","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Leza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research)  Madrid Spain"},{"name":"Biomedical Network Research Center of Mental Health (CIBERSAM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-1416","authenticated-orcid":false,"given":"Elena","family":"Figuero","sequence":"additional","affiliation":[{"name":"ETEP (Etiology and Therapy of Periodontal and Peri\u2010Implant Diseases) Research Group UCM  Madrid Spain"},{"name":"Department of Dental Clinical Specialties, Faculty of Dentistry UCM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Garc\u00eda\u2010Bueno","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research)  Madrid Spain"},{"name":"Biomedical Network Research Center of Mental Health (CIBERSAM) Institute of Health Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12]]},"reference":[{"key":"e_1_2_14_2_1","volume-title":"Global Burden of Mental Disorders and the Need for a Comprehensive, Coordinated Response From Health and Social Sectors at the Country Level: Report by the Secretariat","author":"World Health Assembly","year":"2012"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01738-y"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00638-3"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibror.2018.04.001"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13040646"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21120"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2018.08.021"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.80"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02964-x"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8861903"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01520-y"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02492-0"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.08.048"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-200"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106799"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02287-6"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-03122-4"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153723"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071079"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.814177"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000002347"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.960756"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cre2.70017"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14674"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13420"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13780"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03213-5"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.12.003"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2017.170355"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1690-2"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00082"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03832-8"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13807"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00327"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00483"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.04.040"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2016.00347"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2024.149203"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01468-7"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034406"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0609-8"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.07.002"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.01.001"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(90)90229-W"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109767"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200023"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.02.001"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.802192"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14944"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.08.026"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.10.034"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-024-03680-y"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.105"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2024.115039"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4309-7"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyae010"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2023.02.001"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70669","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:20:20Z","timestamp":1767086420000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":58,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/cns.70669"],"URL":"https:\/\/doi.org\/10.1111\/cns.70669","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70669"}}