{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:45:37Z","timestamp":1792784737934,"version":"4.5.0"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Research Center of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine","id":[{"id":"https:\/\/ror.org\/03qb7bg95","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["82074309"],"award-info":[{"award-number":["82074309"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["82174255"],"award-info":[{"award-number":["82174255"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Late-onset depression (LOD) is a common subtype of depression in the elderly, characterized by high disability and recurrence rates, along with poorly understood biological correlates, posing a serious threat to the health of the aging population; moreover, the molecular correlates and diagnostic targets for LOD remain largely unknown. Aging and stress are recognized as two core risk factors for LOD; however, whether they interact and how such interaction is associated with the depressive phenotype remain unclear, so we established a rat model of LOD to analyze the interactive effects of aging and stress on depressive-like behaviors, and combined this with cerebrospinal fluid proteomics to explore potential protein correlates and provide experimental evidence for identifying candidate therapeutic targets. In terms of results, aging and stress exhibited a synergistic association with depressive-like behaviors in LOD rats, and enrichment was observed in extracellular matrix and sphingolipid metabolic pathways; furthermore, several proteins\u2500including ceramide, MMP2, TIMP2, SPARC, FBN1, and collagen\u2500were identified as candidate correlates worthy of further investigation. In conclusion, stress and aging exert interactive effects on behavioral phenotypes in LOD rats, with associated alterations in extracellular matrix and sphingolipid pathways, and key molecules including Cer, MMP2, Timp2, and Sparc warrant further investigation.<\/jats:p>","DOI":"10.1021\/acs.jproteome.5c01055","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:50:35Z","timestamp":1788292235000},"page":"5062-5074","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Features and Association Analysis of Late-Onset\nDepression Based on Behavioral Factorial Analysis and Proteomics"],"prefix":"10.1021","volume":"25","author":[{"given":"Yuqi","family":"Yan","sequence":"first","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiange","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxin","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital of Traditional Chinese Medicine , , , ,","place":["Shenzhen, Guangdong Province, China, 518000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Fan","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-5099","authenticated-orcid":true,"given":"Can","family":"Yan","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3643-9010","authenticated-orcid":true,"given":"Lili","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine , , , ,","place":["Guangzhou, Guangdong Province, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"issue":"3","key":"2026100208414903200_cit1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/gerona\/58.3.m249","article-title":"Depression\nin late life: review and commentary","volume":"58","author":"Blazer","year":"2003","journal-title":"J. Gerontol.,\nSer. A"},{"issue":"4","key":"2026100208414903200_cit2","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.jagp.2023.01.002","article-title":"Does Late-Life\nDepression Accelerate Aging?","volume":"31","author":"Lavretsky","year":"2023","journal-title":"Am. J. Geriatr.\nPsychiatry"},{"issue":"7","key":"2026100208414903200_cit3","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.exger.2012.08.011","article-title":"PPARgamma and stress:\nimplications for aging","volume":"48","author":"Ulrich-Lai","year":"2013","journal-title":"Exp. Gerontol."},{"key":"2026100208414903200_cit4","doi-asserted-by":"publisher","first-page":"101805","DOI":"10.1016\/j.arr.2022.101805","article-title":"Major depression and\nthe biological hallmarks of aging","volume":"83","author":"Lorenzo","year":"2023","journal-title":"Ageing Res.\nRev."},{"issue":"6","key":"2026100208414903200_cit5","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20199356","article-title":"Proteome\nprofiling in cerebrospinal fluid reveals\nnovel biomarkers of Alzheimer\u2019s disease","volume":"16","author":"Bader","year":"2020","journal-title":"Mol. Syst. Biol."},{"issue":"43","key":"2026100208414903200_cit6","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz9360","article-title":"Integrated proteomics reveals brain-based cerebrospinal\nfluid biomarkers in asymptomatic and symptomatic Alzheimer\u2019s\ndisease","volume":"6","author":"Higginbotham","year":"2020","journal-title":"Sci. Adv."},{"key":"2026100208414903200_cit7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.psyneuen.2019.05.007","article-title":"Chronic mild stress\nleads to aberrant glucose energy metabolism in depressed Macaca fascicularis\nmodels","volume":"107","author":"Qin","year":"2019","journal-title":"Psychoneuroendocrinology"},{"issue":"1","key":"2026100208414903200_cit8","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41398-020-0825-7","article-title":"Proteomic analysis reveals a biosignature of decreased synaptic protein\nin cerebrospinal fluid of major depressive disorder","volume":"10","author":"Al Shweiki","year":"2020","journal-title":"Transl. 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Psychiatry"},{"issue":"12","key":"2026100208414903200_cit27","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1038\/npp.2011.153","article-title":"Overexpression of Reelin\nprevents the manifestation of behavioral phenotypes related to schizophrenia\nand bipolar disorder","volume":"36","author":"Teixeira","year":"2011","journal-title":"Neuropsychopharmacology"},{"issue":"2","key":"2026100208414903200_cit28","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.cell.2020.05.050","article-title":"Microglial Remodeling\nof the Extracellular Matrix Promotes Synapse Plasticity","volume":"182","author":"Nguyen","year":"2020","journal-title":"Cell"},{"issue":"4","key":"2026100208414903200_cit29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1017\/neu.2015.72","article-title":"The role of MMP genes\nin recurrent depressive disorders and cognitive functions","volume":"28","author":"Bobinska","year":"2016","journal-title":"Acta Neuropsychiatr"},{"issue":"9","key":"2026100208414903200_cit30","doi-asserted-by":"publisher","first-page":"pyw019","DOI":"10.1093\/ijnp\/pyw019","article-title":"Altered Serum Levels of Matrix Metalloproteinase-2,\n\u22129 in Response to Electroconvulsive Therapy for Mood Disorders","volume":"19","author":"Shibasaki","year":"2016","journal-title":"Int. J. Neuropsychopharmacol."},{"issue":"11","key":"2026100208414903200_cit31","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/ijnp\/pyaa049","article-title":"Increased matrix metalloproteinases\nin cerebrospinal fluids of patients with major depressive disorder\nand schizophrenia","volume":"23","author":"Omori","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"2026100208414903200_cit32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3389\/fncel.2019.00197","article-title":"Chronic Stress Modulates\nInterneuronal Plasticity: Effects on PSA-NCAM and Perineuronal Nets\nin Cortical and Extracortical Regions","volume":"13","author":"Pesarico","year":"2019","journal-title":"Front.\nCell. Neurosci."},{"key":"2026100208414903200_cit33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.neubiorev.2020.07.015","article-title":"Incubation\nof depression: ECM assembly\nand parvalbumin interneurons after stress","volume":"118","author":"Spijker","year":"2020","journal-title":"Neurosci.\nBiobehav. Rev."},{"key":"2026100208414903200_cit34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jad.2017.02.008","article-title":"Ceramides\nand depression: A systematic\nreview","volume":"213","author":"Dinoff","year":"2017","journal-title":"J. Affective Disord."},{"key":"2026100208414903200_cit35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.metabol.2019.04.002","article-title":"Targeted\nlipidomics\nreveal derangement of ceramides in major depression and bipolar disorder","volume":"95","author":"Brunkhorst-Kanaan","year":"2019","journal-title":"Metabolism"},{"issue":"8","key":"2026100208414903200_cit36","doi-asserted-by":"publisher","first-page":"102185","DOI":"10.1016\/j.jbc.2022.102185","article-title":"Ceramide levels in blood\nplasma correlate with major depressive disorder severity and its neutralization\nabrogates depressive behavior in mice","volume":"298","author":"Schumacher","year":"2022","journal-title":"J. Biol.\nChem."},{"issue":"6","key":"2026100208414903200_cit37","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1111\/jnc.15759","article-title":"Contribution of ceramides metabolism\nin psychiatric disorders","volume":"164","author":"Bernal-Vega","year":"2023","journal-title":"J. Neurochem."},{"issue":"6","key":"2026100208414903200_cit38","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13048","article-title":"The role of lipid metabolism\nin aging, lifespan regulation,\nand age-related disease","volume":"18","author":"Johnson","year":"2019","journal-title":"Aging Cell"},{"issue":"45","key":"2026100208414903200_cit39","doi-asserted-by":"publisher","first-page":"11459","DOI":"10.1523\/JNEUROSCI.2351-16.2016","article-title":"Casting a Wide Net:\nRole of Perineuronal Nets in Neural Plasticity","volume":"36","author":"Sorg","year":"2016","journal-title":"J. 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Affective Disord."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.5c01055","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5062\/67510139\/acs.jproteome.5c01055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5062\/67510139\/acs.jproteome.5c01055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:51:39Z","timestamp":1790945499000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/10\/5062\/5339137\/Proteomic-Features-and-Association-Analysis-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,8,27]]},"published-print":{"date-parts":[[2026,10,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.5c01055","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}