{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:48:43Z","timestamp":1782276523421,"version":"3.54.5"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013360","name":"Universidade Do Extremo Sul Catarinense","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013360","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurotox Res"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The present study aimed to investigate the effects of chronic mild stress (CMS) on neurotrophic factors in the brains of rats subjected to the cecal ligation and puncture (CLP) model of sepsis. After 30 days of the CLP procedure, the animals were subjected to CMS. Twenty-four hours after the last stressor, the animals were euthanized, their blood was collected, and their brains were dissected in the frontal cortex and hippocampus. Then, the levels of brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, nerve growth factor, and glial cell line-derived neurotrophic factor were evaluated in the brain structures. The levels of adrenocorticotropic hormone and corticosterone were evaluated in the serum of the rats. The four experimental groups of the present study were: (1) Sham\u2009+\u2009Non-stressed; (2) Sepsis\u2009+\u2009Non-stressed; (3) Sham\u2009+\u2009CMS; (4) Sepsis\u2009+\u2009CMS. CMS increased adrenocorticotropic hormone and corticosterone levels, whereas sepsis alone did not significantly alter these hormones. Regarding neurotrophic factors, CMS reduced the levels of BDNF, NT-3, NT-4, and NGF in both the hippocampus and frontal cortex, regardless of prior sepsis exposure. Sepsis alone was also associated with reduced levels of these neurotrophins, although the magnitude of the effect varied depending on the specific neurotrophin and brain region, with greater reductions observed for BDNF and NGF. No interaction between sepsis and CMS was detected for these neurotrophins, suggesting independent effects. Our findings suggest that sepsis and CMS independently affect most neurotrophin levels, with no clear evidence that prior sepsis potentiates the effects of subsequent CMS. GDNF represents an exception, pointing to potential region-specific mechanisms that warrant further investigation.<\/jats:p>","DOI":"10.1007\/s12640-026-00801-6","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T07:37:58Z","timestamp":1779521878000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Chronic Mild Stress on Neurotrophic and Hypothalamic-Pituitary-Adrenal Factors in the Brain of Rats Submitted to Sepsis"],"prefix":"10.1007","volume":"44","author":[{"given":"Jeft\u00e9","family":"Peper-Nascimento","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taise","family":"Possamai-Della","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Gois-Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge M.","family":"Aguiar-Geraldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Pescador","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Quevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Dal-Pizzol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira S.","family":"Valvassori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"801_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.33696\/immunology.5.183","volume":"5","author":"TA Addissouky","year":"2023","unstructured":"Addissouky TA, El Sayed TE, Ali I MMA, et al (2023) Molecular pathways in sepsis pathogenesis: recent advances and therapeutic avenues. J Cell Immunol 5:174\u2013183. https:\/\/doi.org\/10.33696\/immunology.5.183","journal-title":"J Cell Immunol"},{"key":"801_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s12640-024-00727-x","volume":"43","author":"JM Aguiar-Geraldo","year":"2025","unstructured":"Aguiar-Geraldo JM, Canever L, Marino DP et al (2025) Exploring the different impacts of ketamine on neurotrophic factors and inflammatory parameters in a cecal ligation and puncture-induced sepsis model. Neurotox Res 43:5. https:\/\/doi.org\/10.1007\/s12640-024-00727-x","journal-title":"Neurotox Res"},{"key":"801_CR3","doi-asserted-by":"publisher","unstructured":"Annane D (2016) The role of ACTH and corticosteroids for sepsis and septic shock: an update. Front Endocrinol (Lausanne) 7. https:\/\/doi.org\/10.3389\/fendo.2016.00070","DOI":"10.3389\/fendo.2016.00070"},{"key":"801_CR4","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1590\/S0100-879X2007000600013","volume":"40","author":"T Barichello","year":"2007","unstructured":"Barichello T, Martins MR, Reinke A et al (2007) Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation. Braz J Med Biol Res 40:831\u2013837. https:\/\/doi.org\/10.1590\/S0100-879X2007000600013","journal-title":"Braz J Med Biol Res"},{"key":"801_CR5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","volume":"107","author":"E Beurel","year":"2020","unstructured":"Beurel E, Toups M, Nemeroff CB (2020) The bidirectional relationship of depression and inflammation: double trouble. Neuron 107:234\u2013256. https:\/\/doi.org\/10.1016\/j.neuron.2020.06.002","journal-title":"Neuron"},{"key":"801_CR6","doi-asserted-by":"crossref","unstructured":"Bothwell M (2014) NGF, BDNF, NT3, and NT4. pp 3\u201315","DOI":"10.1007\/978-3-642-45106-5_1"},{"key":"801_CR7","first-page":"629","volume":"92","author":"C Caraballo","year":"2019","unstructured":"Caraballo C, Jaimes F (2019) Organ dysfunction in sepsis: an ominous trajectory from infection to death. Yale J Biol Med 92:629\u2013640","journal-title":"Yale J Biol Med"},{"key":"801_CR8","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.yhbeh.2015.11.006","volume":"78","author":"J Chen","year":"2016","unstructured":"Chen J, Wang Z, Zuo W et al (2016) Effects of chronic mild stress on behavioral and neurobiological parameters \u2014 Role of glucocorticoid. Horm Behav 78:150\u2013159. https:\/\/doi.org\/10.1016\/j.yhbeh.2015.11.006","journal-title":"Horm Behav"},{"key":"801_CR9","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1002\/syn.21760","volume":"68","author":"CM Comim","year":"2014","unstructured":"Comim CM, Silva NC, Mina F et al (2014) Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis. Synapse 68:474\u2013479. https:\/\/doi.org\/10.1002\/syn.21760","journal-title":"Synapse"},{"key":"801_CR10","doi-asserted-by":"publisher","first-page":"5247","DOI":"10.1007\/s12035-020-02089-9","volume":"57","author":"LG Danielski","year":"2020","unstructured":"Danielski LG, Giustina A, Della, Bonfante S et al (2020) NLRP3 Activation contributes to acute brain damage leading to memory impairment in sepsis-surviving rats. Mol Neurobiol 57:5247\u20135262. https:\/\/doi.org\/10.1007\/s12035-020-02089-9","journal-title":"Mol Neurobiol"},{"key":"801_CR11","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1159\/000520746","volume":"29","author":"NN dos Santos-Junior","year":"2022","unstructured":"dos Santos-Junior NN, da Costa LHA, Catal\u00e3o CHR, Alves Rocha MJ (2022) Corticosterone and adrenocorticotrophic hormone secretion is recovered after immune challenge or acute restraint stress in sepsis survivor animals. Neuroimmunomodulation 29:306\u2013316. https:\/\/doi.org\/10.1159\/000520746","journal-title":"Neuroimmunomodulation"},{"key":"801_CR12","doi-asserted-by":"publisher","first-page":"105097","DOI":"10.1016\/j.psyneuen.2020.105097","volume":"124","author":"H Eliwa","year":"2021","unstructured":"Eliwa H, Brizard B, Le Guisquet A-M et al (2021) Adult neurogenesis augmentation attenuates anhedonia and HPA axis dysregulation in a mouse model of chronic stress and depression. Psychoneuroendocrinology 124:105097. https:\/\/doi.org\/10.1016\/j.psyneuen.2020.105097","journal-title":"Psychoneuroendocrinology"},{"key":"801_CR13","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.neuroscience.2014.12.048","volume":"289","author":"CB Filho","year":"2015","unstructured":"Filho CB, Jesse CR, Donato F et al (2015) Chronic unpredictable mild stress decreases BDNF and NGF levels and Na+,K+-ATPase activity in the hippocampus and prefrontal cortex of mice: Antidepressant effect of chrysin. Neuroscience 289:367\u2013380. https:\/\/doi.org\/10.1016\/j.neuroscience.2014.12.048","journal-title":"Neuroscience"},{"key":"801_CR14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s12031-012-9872-8","volume":"50","author":"M First","year":"2013","unstructured":"First M, Gil-Ad I, Taler M et al (2013) The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress. J Mol Neurosci 50:88\u201397. https:\/\/doi.org\/10.1007\/s12031-012-9872-8","journal-title":"J Mol Neurosci"},{"key":"801_CR15","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/2110-5820-1-53","volume":"1","author":"MA Flierl","year":"2011","unstructured":"Flierl MA, Rittirsch D, Weckbach S et al (2011) Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis. Ann Intensive Care 1:53. https:\/\/doi.org\/10.1186\/2110-5820-1-53","journal-title":"Ann Intensive Care"},{"key":"801_CR16","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s12974-024-03084-w","volume":"21","author":"Q Fu","year":"2024","unstructured":"Fu Q, Zhang Y-B, Shi C-X et al (2024) GSDMD\/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy. J Neuroinflammation 21:96. https:\/\/doi.org\/10.1186\/s12974-024-03084-w","journal-title":"J Neuroinflammation"},{"key":"801_CR17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0197-0186(02)00080-3","volume":"42","author":"GD Gamaro","year":"2003","unstructured":"Gamaro GD, Manoli LP, Torres ILS et al (2003) Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures. Neurochem Int 42:107\u2013114. https:\/\/doi.org\/10.1016\/S0197-0186(02)00080-3","journal-title":"Neurochem Int"},{"key":"801_CR18","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000520281","volume":"89","author":"L-L Gao","year":"2022","unstructured":"Gao L-L, Wang Z-H, Mu Y-H et al (2022) Emodin promotes autophagy and prevents apoptosis in sepsis-associated encephalopathy through activating BDNF\/TrkB signaling. Pathobiology 89:135\u2013145. https:\/\/doi.org\/10.1159\/000520281","journal-title":"Pathobiology"},{"key":"801_CR19","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.2147\/JIR.S400115","volume":"16","author":"LF Garcia","year":"2023","unstructured":"Garcia LF, Singh V, Mireles B et al (2023) Common variables that influence sepsis mortality in mice. J Inflamm Res Volume 16:1121\u20131134. https:\/\/doi.org\/10.2147\/JIR.S400115","journal-title":"J Inflamm Res Volume"},{"key":"801_CR20","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.pnpbp.2009.01.004","volume":"33","author":"LSB Garcia","year":"2009","unstructured":"Garcia LSB, Comim CM, Valvassori SS et al (2009) Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 33:450\u2013455. https:\/\/doi.org\/10.1016\/j.pnpbp.2009.01.004","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"801_CR21","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1073\/pnas.1210200110","volume":"110","author":"JE Goodwin","year":"2013","unstructured":"Goodwin JE, Feng Y, Velazquez H, Sessa WC (2013) Endothelial glucocorticoid receptor is required for protection against sepsis. Proc Natl Acad Sci 110:306\u2013311. https:\/\/doi.org\/10.1073\/pnas.1210200110","journal-title":"Proc Natl Acad Sci"},{"key":"801_CR22","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1016\/j.ymthe.2024.05.001","volume":"32","author":"B Gr\u00fcnewald","year":"2024","unstructured":"Gr\u00fcnewald B, Wickel J, Hahn N et al (2024) Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy. Mol Ther 32:2113\u20132129. https:\/\/doi.org\/10.1016\/j.ymthe.2024.05.001","journal-title":"Mol Ther"},{"key":"801_CR23","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/s41419-025-07469-4","volume":"16","author":"C Guo","year":"2025","unstructured":"Guo C, Li W, Liu Y et al (2025) LCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments. Cell Death Dis 16:146. https:\/\/doi.org\/10.1038\/s41419-025-07469-4","journal-title":"Cell Death Dis"},{"key":"801_CR24","doi-asserted-by":"publisher","unstructured":"Hoshino K (2025) Targeting synaptic plasticity to bridge translational gaps in sepsis-associated encephalopathy. Front Aging Neurosci 17. https:\/\/doi.org\/10.3389\/fnagi.2025.1616736","DOI":"10.3389\/fnagi.2025.1616736"},{"key":"801_CR25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1097\/01.shk.0000191414.94461.7e","volume":"24","author":"WJ Hubbard","year":"2005","unstructured":"Hubbard WJ, Choudhry M, Schwacha MG et al (2005) Cecal ligation and puncture. Shock 24:52\u201357. https:\/\/doi.org\/10.1097\/01.shk.0000191414.94461.7e","journal-title":"Shock"},{"key":"801_CR26","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1001\/jama.2010.1553","volume":"304","author":"TJ Iwashyna","year":"2010","unstructured":"Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304:1787. https:\/\/doi.org\/10.1001\/jama.2010.1553","journal-title":"JAMA"},{"key":"801_CR27","doi-asserted-by":"publisher","first-page":"102516","DOI":"10.1016\/j.npep.2025.102516","volume":"111","author":"MN Khan","year":"2025","unstructured":"Khan MN, Choudhary D, Mehan S, Khan Z, Gupta GD, Narula AS (2025) Molecular mechanisms of GDNF\/GFRA1\/RET and PI3K\/AKT\/ERK signaling interplay in neuroprotection: therapeutic strategies for treating neurological disorders. Neuropeptides 111:102516. https:\/\/doi.org\/10.1016\/j.npep.2025.102516","journal-title":"Neuropeptides"},{"key":"801_CR28","doi-asserted-by":"publisher","first-page":"4855","DOI":"10.3390\/nu15234855","volume":"15","author":"C-Y Kim","year":"2023","unstructured":"Kim C-Y, Ko K, Choi S-H et al (2023) Effects of saffron extract (Affron\u00ae) with 100 mg\/kg and 200 mg\/kg on hypothalamic\u2013pituitary\u2013adrenal axis and stress resilience in chronic mild stress-induced depression in wistar rats. Nutrients 15:4855. https:\/\/doi.org\/10.3390\/nu15234855","journal-title":"Nutrients"},{"issue":"4","key":"801_CR29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3390\/biology9040063","volume":"9","author":"EM Kozlov","year":"2020","unstructured":"Kozlov EM, Grechko AV, Chegodaev YS, Wu WK, Orekhov AN (2020) Contribution of neurotrophins to the immune system regulation and possible connection to alcohol addiction. Biology 9(4):63. https:\/\/doi.org\/10.3390\/biology9040063","journal-title":"Biology"},{"key":"801_CR30","doi-asserted-by":"publisher","first-page":"3093","DOI":"10.1007\/s10072-024-07409-8","volume":"45","author":"D Li","year":"2024","unstructured":"Li D, Zhang X, Lu Y et al (2024) Post-sepsis psychiatric disorder: pathophysiology, prevention, and treatment. Neurol Sci 45:3093\u20133105. https:\/\/doi.org\/10.1007\/s10072-024-07409-8","journal-title":"Neurol Sci"},{"key":"801_CR31","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265\u2013275","journal-title":"J Biol Chem"},{"key":"801_CR52","doi-asserted-by":"publisher","unstructured":"Mishra BR, Maiti R, Nath S, Sahoo P, Jena M, Mishra A (2019) Effect of Sertraline, Dosulepin, and Venlafaxine on Non-BDNF Neurotrophins in Patients With Depression: A Cohort Study. J Clin Psychopharmacol, 39(3), 220\u2013225. https:\/\/doi.org\/10.1097\/JCP.0000000000001022","DOI":"10.1097\/JCP.0000000000001022"},{"key":"801_CR32","doi-asserted-by":"publisher","unstructured":"Nandam LS, Brazel M, Zhou M, Jhaveri DJ (2020) Cortisol and major depressive disorder\u2014translating findings from humans to animal models and back. Front Psychiatry 10. https:\/\/doi.org\/10.3389\/fpsyt.2019.00974","DOI":"10.3389\/fpsyt.2019.00974"},{"key":"801_CR33","doi-asserted-by":"publisher","unstructured":"PanS, Lv Z, Wang R et al (2022) Sepsis-induced brain dysfunction: pathogenesis, diagnosis, and treatment. Oxid Med Cell Longev https:\/\/doi.org\/10.1155\/2022\/1328729","DOI":"10.1155\/2022\/1328729"},{"key":"801_CR34","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1007\/s10753-020-01187-z","volume":"43","author":"M Pereira de Souza Goldim","year":"2020","unstructured":"Pereira de Souza Goldim M, Della Giustina A, Mathias K et al (2020) Sickness behavior score is associated with neuroinflammation and late behavioral changes in polymicrobial sepsis animal model. Inflammation 43:1019\u20131034. https:\/\/doi.org\/10.1007\/s10753-020-01187-z","journal-title":"Inflammation"},{"key":"801_CR35","doi-asserted-by":"publisher","first-page":"1618330","DOI":"10.3389\/fphys.2025.1618330","volume":"16","author":"C Porcari","year":"2025","unstructured":"Porcari C, Cattaneo S, Crippa L, Simonato M, Bettegazzi B (2025) Exploring the diversity of biological processes regulated by glial cell line-derived neurotrophic factor, a pleiotropic molecule with therapeutic potential. Front Physiol 16:1618330. https:\/\/doi.org\/10.3389\/fphys.2025.1618330","journal-title":"Front Physiol"},{"key":"801_CR36","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00441-018-02985-6","volume":"377","author":"T Rantam\u00e4ki","year":"2019","unstructured":"Rantam\u00e4ki T (2019) TrkB neurotrophin receptor at the core of antidepressant effects, but how? Cell Tissue Res 377:115\u2013124. https:\/\/doi.org\/10.1007\/s00441-018-02985-6","journal-title":"Cell Tissue Res"},{"key":"801_CR37","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1016\/S0140-6736(20)32535-6","volume":"396","author":"KE Rudd","year":"2020","unstructured":"Rudd KE, Ikuta KS, Naghavi M (2020) Sepsis \u2013 Authors\u2019 reply. Lancet 396:1805\u20131806. https:\/\/doi.org\/10.1016\/S0140-6736(20)32535-6","journal-title":"Lancet"},{"issue":"24","key":"801_CR38","doi-asserted-by":"publisher","first-page":"6968","DOI":"10.1046\/j.1432-1327.2000.01826.x","volume":"267","author":"M Saarma","year":"2000","unstructured":"Saarma M (2000) GDNF - a stranger in the TGF-beta superfamily? Eur J Biochem 267(24):6968\u20136971. https:\/\/doi.org\/10.1046\/j.1432-1327.2000.01826.x","journal-title":"Eur J Biochem"},{"key":"801_CR39","doi-asserted-by":"publisher","unstructured":"Sakr Y, Jaschinski U, Wittebole X et al (2018) Sepsis in intensive care unit patients: worldwide data from the intensive care over nations audit. Open Forum Infect Dis 5. https:\/\/doi.org\/10.1093\/ofid\/ofy313","DOI":"10.1093\/ofid\/ofy313"},{"key":"801_CR40","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801. https:\/\/doi.org\/10.1001\/jama.2016.0287","journal-title":"JAMA"},{"key":"801_CR41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jpsychires.2017.06.006","volume":"94","author":"AV Steckert","year":"2017","unstructured":"Steckert AV, Dominguini D, Michels M et al (2017) The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis. J Psychiatr Res 94:47\u201353. https:\/\/doi.org\/10.1016\/j.jpsychires.2017.06.006","journal-title":"J Psychiatr Res"},{"key":"801_CR42","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1080\/14787210.2020.1812384","volume":"19","author":"SC Tauber","year":"2021","unstructured":"Tauber SC, Djukic M, Gossner J et al (2021) Sepsis-associated encephalopathy and septic encephalitis: an update. Expert Rev Anti Infect Ther 19:215\u2013231. https:\/\/doi.org\/10.1080\/14787210.2020.1812384","journal-title":"Expert Rev Anti Infect Ther"},{"key":"801_CR43","doi-asserted-by":"publisher","first-page":"173992","DOI":"10.1016\/j.ejphar.2021.173992","volume":"898","author":"VN Thakare","year":"2021","unstructured":"Thakare VN, Lakade SH, Mahajan MP et al (2021) Protocatechuic acid attenuates chronic unpredictable mild stress induced-behavioral and biochemical alterations in mice. Eur J Pharmacol 898:173992. https:\/\/doi.org\/10.1016\/j.ejphar.2021.173992","journal-title":"Eur J Pharmacol"},{"key":"801_CR44","doi-asserted-by":"publisher","unstructured":"Vandewalle J, Libert C (2020) Glucocorticoids in Sepsis: To Be or Not to Be. Front Immunol 11: https:\/\/doi.org\/10.3389\/fimmu.2020.01318","DOI":"10.3389\/fimmu.2020.01318"},{"key":"801_CR45","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.2174\/13894501113149990208","volume":"14","author":"F Walker","year":"2013","unstructured":"Walker F, Nilsson M, Jones K (2013) Acute and Chronic Stress-Induced Disturbances of Microglial Plasticity, Phenotype and Function. Curr Drug Targets 14:1262\u20131276. https:\/\/doi.org\/10.2174\/13894501113149990208","journal-title":"Curr Drug Targets"},{"key":"801_CR46","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ynstr.2016.08.002","volume":"6","author":"P Willner","year":"2017","unstructured":"Willner P (2017) The chronic mild stress (CMS) model of depression: history, evaluation and usage. Neurobiol Stress 6:78\u201393. https:\/\/doi.org\/10.1016\/j.ynstr.2016.08.002","journal-title":"Neurobiol Stress"},{"key":"801_CR47","doi-asserted-by":"publisher","first-page":"117200","DOI":"10.1016\/j.biopha.2024.117200","volume":"178","author":"K Xu","year":"2024","unstructured":"Xu K, Huang Q, Lyu Y et al (2024) Phosphatidylserine improves aging sepsis survival, modulates gut microbiome, and prevents sepsis-associated encephalopathy. Biomed Pharmacother 178:117200. https:\/\/doi.org\/10.1016\/j.biopha.2024.117200","journal-title":"Biomed Pharmacother"},{"key":"801_CR48","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2174\/1570159X23666241028105746","volume":"23","author":"L Yang","year":"2025","unstructured":"Yang L, Li J, Liu F et al (2025) The biological changes of synaptic plasticity in the pathological process of sepsis-associated encephalopathy. Curr Neuropharmacol 23:359\u2013374. https:\/\/doi.org\/10.2174\/1570159X23666241028105746","journal-title":"Curr Neuropharmacol"},{"key":"801_CR50","doi-asserted-by":"publisher","unstructured":"Yin R, Zhang K, Li Y et al (2023) Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation. Front Immunol 14. https:\/\/doi.org\/10.3389\/fimmu.2023.1181973","DOI":"10.3389\/fimmu.2023.1181973"},{"key":"801_CR51","doi-asserted-by":"publisher","unstructured":"Zeng N, Xu J, Yao W et al (2017) Brain-derived neurotrophic factor attenuates septic myocardial dysfunction via eNOS\/NO pathway in rats. Oxid Med Cell Longev. https:\/\/doi.org\/10.1155\/2017\/1721434","DOI":"10.1155\/2017\/1721434"}],"container-title":["Neurotoxicity Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-026-00801-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-026-00801-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-026-00801-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:17:27Z","timestamp":1782274647000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12640-026-00801-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["801"],"URL":"https:\/\/doi.org\/10.1007\/s12640-026-00801-6","relation":{},"ISSN":["1029-8428","1476-3524"],"issn-type":[{"value":"1029-8428","type":"print"},{"value":"1476-3524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]},"assertion":[{"value":"4 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Conselho Nacional de Controle de Experimenta\u00e7\u00e3o Animal (CONCEA). The local ethics committee approved the present study, Comiss\u00e3o de \u00c9tica no Uso de Animais Experimentais at the University of Southern Santa Catarina (protocol 051-2014-02).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Jo\u00e3o Quevedo reports receiving clinical research support from LivaNova, Neumora Therapeutics, Johnson & Johnson, Alto Neuroscience, and Compass Pathways. He also reports non-industry research support from Brigham and Women\u2019s Hospital, the John S. Dunn Foundation, and the National Network of Depression Centers. He has received consulting fees from LivaNova, speaker honoraria from Intra-Cellular Therapies and EMS, and royalties or copyright-related income from Grupo A\/Artmed and Elsevier\/Academic Press. All relationships are outside the submitted work. The other authors declare no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}