{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:19:51Z","timestamp":1791656391486,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shaanxi Provincial Fund General Project","award":["2021JM-211"],"award-info":[{"award-number":["2021JM-211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Objective: This study aimed to investigate the effect of exercise on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) in rats and to explore the role of the SIRT3\/ROS\/NLRP3 signaling pathway in this process. Methods: Twenty-nine male 8-week-old Sprague Dawley rats were divided into a control group (CON) (nine rats) and a model group (twenty rats). Thirteen chronic stress stimuli were randomly applied once or twice per day for 35 days to induce depression in the model group rats. After the model was established, the model group rats were randomly divided into the CUMS group (CUMS) and the aerobic exercise + CUMS group (EX + CUMS). The EX + CUMS group received 8 weeks of aerobic exercise intervention for 6 days per week. Behavioral assessments were performed using the sucrose preference test and forced swimming test. The expression of SIRT3, NLRP3, IL-1\u03b2, and IL-18 in the hippocampus was detected using RT-PCR. The ROS level in the hippocampus was detected using immunofluorescence. The protein levels of SIRT3 and NLRP3 in the hippocampus were detected using western blotting. The protein levels of IL-1\u03b2 and IL-18 in the hippocampus were measured using ELISA. Results: After 5 weeks of chronic stress stimuli, the hippocampal function of rats in the CUMS model group was impaired, and their sucrose preference was reduced, while their forced swimming time was prolonged. The expression of SIRT3 decreased, ROS increased, and the expression of NLRP3 and the levels of IL-1\u03b2 and IL-18 increased. Aerobic exercise increased the sucrose preference of rats, shortened their immobility time, increased the expression of SIRT3, and reduced the levels of ROS, NLRP3, IL-1\u03b2, and IL-18. Conclusion: Exercise can improve the depressive behavior of CUMS model rats, and its mechanism may be related to the upregulation of SIRT3 in the hippocampus, which plays an anti-inflammatory role.<\/jats:p>","DOI":"10.3390\/life13081711","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:08:59Z","timestamp":1691575739000},"page":"1711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Aerobic Exercise Improves Depressive-like Behavior in CUMS-Induced Rats via the SIRT3\/ROS\/NLRP3 Signaling Pathway"],"prefix":"10.3390","volume":"13","author":[{"given":"Lijun","family":"Wang","sequence":"first","affiliation":[{"name":"School of Physical Education, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Physical Education, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Physical Education, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.specom.2015.03.004","article-title":"A review of depression and suicide risk assessment using speech analysis","volume":"71","author":"Cummins","year":"2015","journal-title":"Speech Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neubiorev.2019.07.021","article-title":"Depression biomarkers using non-invasive EEG: A review","volume":"105","author":"Rosa","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0140-6736(19)30934-1","article-title":"New WHO prevalence estimates of mental disorders in conflict settings: A systematic review and meta-analysis","volume":"394","author":"Charlson","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/da.22217","article-title":"Major depressive disorder in DSM-5: Implications for clinical practice and research of changes from DSM-IV","volume":"31","author":"Uher","year":"2014","journal-title":"Depress. Anxiety"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S0140-6736(22)01012-1","article-title":"Depression in young people","volume":"400","author":"Thapar","year":"2022","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jpsychires.2019.08.002","article-title":"Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study","volume":"126","author":"Liu","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1080\/10408398.2013.876960","article-title":"The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors","volume":"56","author":"Du","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1037\/a0035302","article-title":"From stress to inflammation and major depressive disorder: A social signal transduction theory of depression","volume":"140","author":"Slavich","year":"2014","journal-title":"Psychol. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fpsyt.2015.00032","article-title":"Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?","volume":"6","author":"Du","year":"2015","journal-title":"Front. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1038\/s41380-022-01520-y","article-title":"Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications","volume":"27","author":"Tartt","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dey, A., and Hankey, G.P. (2018). Insights into Macrophage Heterogeneity and Cytokine-Induced Neuroinflammation in Major Depressive Disorder. Pharmaceuticals, 11.","DOI":"10.3390\/ph11030064"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41398-019-0521-7","article-title":"Biomarkers for response in major depression: Comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies","volume":"9","author":"Carboni","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kuhn, M., Hoger, N., Feige, B., Blechert, J., Normann, C., and Nissen, C. (2014). Fear extinction as a model for synaptic plasticity in major depressive disorder. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115280"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.nbd.2018.02.016","article-title":"NLRP3-dependent synaptic plasticity deficit in an Alzheimer\u2019s disease amyloidosis model in vivo","volume":"114","author":"Qi","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nrd.2018.97","article-title":"Targeting the NLRP3 inflammasome in inflammatory diseases","volume":"17","author":"Mangan","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fnmol.2018.00320","article-title":"Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases","volume":"11","author":"Shao","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-020-02040-8","article-title":"Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a\/SYK\/NF-kappaB axis","volume":"18","author":"Li","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12515","DOI":"10.1096\/fj.201802805RR","article-title":"Activation of ROS\/MAPKs\/NF-kappaB\/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis","volume":"33","author":"An","year":"2019","journal-title":"Faseb J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2183026","DOI":"10.1155\/2016\/2183026","article-title":"ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia\/Reperfusion Injury","volume":"2016","author":"Minutoli","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/jmcb\/mjaa074","article-title":"Sirt3 is critical for p53-mediated ferroptosis upon ROS-induced stress","volume":"13","author":"Jin","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3389\/fnins.2018.00414","article-title":"Sirt3 Ameliorates Oxidative Stress and Mitochondrial Dysfunction After Intracerebral Hemorrhage in Diabetic Rats","volume":"12","author":"Zheng","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113144","DOI":"10.1016\/j.expneurol.2019.113144","article-title":"NAD(+) precursor modulates post-ischemic mitochondrial fragmentation and reactive oxygen species generation via SIRT3 dependent mechanisms","volume":"325","author":"Klimova","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jshs.2020.01.004","article-title":"Physical exercise in the prevention and treatment of Alzheimer\u2019s disease","volume":"9","author":"Millan","year":"2020","journal-title":"J. Sport Health Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1849428","DOI":"10.1155\/2021\/1849428","article-title":"High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice","volume":"2021","author":"Luo","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jia, L.L., Kang, Y.M., Wang, F.X., Li, H.B., Zhang, Y., Yu, X.J., Qi, J., Suo, Y.P., Tian, Z.J., and Zhu, Z. (2014). Exercise training attenuates hypertension and cardiac hypertrophy by modulating neurotransmitters and cytokines in hypothalamic paraventricular nucleus. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085481"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jad.2017.10.019","article-title":"Swimming exercise reverses CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins","volume":"227","author":"Liu","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"577062","DOI":"10.3389\/fphar.2020.577062","article-title":"alpha-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3\/ROS Mediated NLRP3 Inflammasome Deactivation","volume":"11","author":"Xia","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","article-title":"Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability","volume":"99","author":"Antoniuk","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_30","first-page":"e52587","article-title":"The forced swim test as a model of depressive-like behavior","volume":"97","author":"Franko","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/jcsm.12322","article-title":"Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure","volume":"9","author":"Tsuda","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"771","DOI":"10.18632\/aging.100075","article-title":"Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle","volume":"1","author":"Palacios","year":"2009","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e12879","DOI":"10.14814\/phy2.12879","article-title":"The effect of acute and chronic sprint-interval training on LRP130, SIRT3, and PGC-1alpha expression in human skeletal muscle","volume":"4","author":"Edgett","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4079041","DOI":"10.1155\/2018\/4079041","article-title":"Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice","volume":"2018","author":"Zhao","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Casuso, R.A., Plaza-Diaz, J., Ruiz-Ojeda, F.J., Aragon-Vela, J., Robles-Sanchez, C., Nordsborg, N.B., Hebberecht, M., Salmeron, L.M., and Huertas, J.R. (2017). High-intensity high-volume swimming induces more robust signaling through PGC-1alpha and AMPK activation than sprint interval swimming in m. triceps brachii. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185494"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1113\/EP085744","article-title":"SIRT3 gene expression but not SIRT3 subcellular localization is altered in response to fasting and exercise in human skeletal muscle","volume":"101","author":"Edgett","year":"2016","journal-title":"Exp. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhou, L., Pinho, R., Gu, Y., and Radak, Z. (2022). The Role of SIRT3 in Exercise and Aging. Cells, 11.","DOI":"10.3390\/cells11162596"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e006347","DOI":"10.1161\/JAHA.117.006347","article-title":"Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway","volume":"6","author":"Chen","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41401-020-0490-7","article-title":"Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation","volume":"42","author":"Song","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","article-title":"The Bidirectional Relationship of Depression and Inflammation: Double Trouble","volume":"107","author":"Beurel","year":"2020","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Berk, M., Williams, L.J., Jacka, F.N., O\u2019Neil, A., Pasco, J.A., Moylan, S., Allen, N.B., Stuart, A.L., Hayley, A.C., and Byrne, M.L. (2013). So depression is an inflammatory disease, but where does the inflammation come from?. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-200"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/PSY.0b013e3181907c1b","article-title":"Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis","volume":"71","author":"Howren","year":"2009","journal-title":"Psychosom. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1113\/JP281356","article-title":"Interpreting \u2018anti-inflammatory\u2019 cytokine responses to exercise: Focus on interleukin-10","volume":"599","author":"Islam","year":"2021","journal-title":"J. Physiol. Lond."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.21037\/atm-22-5443","article-title":"Aerobic exercise reverses the NF-kappaB\/NLRP3 inflammasome\/5-HT pathway by upregulating irisin to alleviate post-stroke depression","volume":"10","author":"Tang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/1535370215619707","article-title":"Possible involvement of the JAK\/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects","volume":"241","author":"Hasan","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/revneuro-2018-0027","article-title":"Therapeutic potential of JAK\/STAT pathway modulation in mood disorders","volume":"30","author":"Shariq","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112545","DOI":"10.1016\/j.biopha.2021.112545","article-title":"Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression","volume":"146","author":"Behl","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8596903","DOI":"10.1155\/2018\/8596903","article-title":"Role and Possible Mechanisms of Sirt1 in Depression","volume":"2018","author":"Lu","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/ni.3772","article-title":"Limiting inflammation-the negative regulation of NF-kappaB and the NLRP3 inflammasome","volume":"18","author":"Afonina","year":"2017","journal-title":"Nat. Immunol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:28:41Z","timestamp":1760128121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["life13081711"],"URL":"https:\/\/doi.org\/10.3390\/life13081711","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]}}}