{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:31:58Z","timestamp":1789468318123,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Major Projects of the National Natural Science Foundation of China","award":["82293651"],"award-info":[{"award-number":["82293651"]}]},{"name":"the Major Projects of the National Natural Science Foundation of China","award":["82130055"],"award-info":[{"award-number":["82130055"]}]},{"name":"the Major Projects of the National Natural Science Foundation of China","award":["82072109"],"award-info":[{"award-number":["82072109"]}]},{"name":"the Key Projects of the National Natural Science Foundation of China","award":["82293651"],"award-info":[{"award-number":["82293651"]}]},{"name":"the Key Projects of the National Natural Science Foundation of China","award":["82130055"],"award-info":[{"award-number":["82130055"]}]},{"name":"the Key Projects of the National Natural Science Foundation of China","award":["82072109"],"award-info":[{"award-number":["82072109"]}]},{"name":"the National Natural Science Foundation of China","award":["82293651"],"award-info":[{"award-number":["82293651"]}]},{"name":"the National Natural Science Foundation of China","award":["82130055"],"award-info":[{"award-number":["82130055"]}]},{"name":"the National Natural Science Foundation of China","award":["82072109"],"award-info":[{"award-number":["82072109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stress-induced alterations in central neuron metabolism and function are crucial contributors to depression onset. However, the metabolic dysfunctions of the neurons associated with depression and specific molecular mechanisms remain unclear. This study initially analyzed the relationship between cholesterol and depression using the NHANES database. We then induced depressive-like behaviors in mice via restraint stress. Applying bioinformatics, pathology, and molecular biology, we observed the pathological characteristics of brain cholesterol homeostasis and investigated the regulatory mechanisms of brain cholesterol metabolism disorders. Through the NHANES database, we initially confirmed a significant correlation between cholesterol metabolism abnormalities and depression. Furthermore, based on successful stress mouse model establishment, we discovered the number of cholesterol-related DEGs significantly increased in the brain due to stress, and exhibited regional heterogeneity. Further investigation of the frontal cortex, a brain region closely related to depression, revealed stress caused significant disruption to key genes related to cholesterol metabolism, including HMGCR, CYP46A1, ACAT1, APOE, ABCA1, and LDLR, leading to an increase in total cholesterol content and a significant decrease in synaptic proteins PSD-95 and SYN. This indicates cholesterol metabolism affects neuronal synaptic plasticity and is associated with stress-induced depressive-like behavior in mice. Adeno-associated virus interference with NR3C1 in the prefrontal cortex of mice subjected to short-term stress resulted in reduced protein levels of NRIP1, NR1H2, ABCA1, and total cholesterol content. At the same time, it increased synaptic proteins PSD95 and SYN, effectively alleviating depressive-like behavior. Therefore, these results suggest that short-term stress may induce cholesterol metabolism disorders by activating the NR3C1\/NRIP1\/NR1H2 signaling pathway. This impairs neuronal synaptic plasticity and consequently participates in depressive-like behavior in mice. These findings suggest that abnormal cholesterol metabolism in the brain induced by stress is a significant contributor to depression onset.<\/jats:p>","DOI":"10.3390\/ijms25158075","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T15:47:32Z","timestamp":1721836052000},"page":"8075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Regulation of Frontal Cortex Cholesterol Metabolism Abnormalities by NR3C1\/NRIP1\/NR1H2 Is Involved in the Occurrence of Stress-Induced Depression"],"prefix":"10.3390","volume":"25","author":[{"given":"Rui","family":"Shi","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmin","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Xin","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical 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refine the genetic architecture of major depression","volume":"50","author":"Wray","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"114725","DOI":"10.1016\/j.psychres.2022.114725","article-title":"Peripheral blood inflammatory markers in depression: Response to electroconvulsive therapy and relationship with cognitive performance","volume":"315","author":"Ryan","year":"2022","journal-title":"Psychiatry Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1001\/jamapsychiatry.2023.0702","article-title":"Effect of Brief Interpersonal Therapy on Depression During Pregnancy A Randomized Clinical Trial","volume":"80","author":"Hankin","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S2215-0366(20)30099-7","article-title":"Review of dysthymia and persistent depressive disorder: History, correlates, and clinical implications","volume":"7","author":"Schramm","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-psych-122216-011613","article-title":"Depression\u2019s Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome","volume":"71","author":"Rea","year":"2020","journal-title":"Annu. Rev. Psychol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"336","DOI":"10.4103\/1673-5374.377587","article-title":"Adverse effects of early-life stress: Focus on the rodent neuroendocrine system","volume":"19","author":"Lee","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1111\/jcpp.13891","article-title":"Research Review: Psychological and psychosocial interventions for children and adolescents with depression, anxiety, and post-traumatic stress disorder in low- and middle-income countries\u2014A systematic review and meta-analysis","volume":"64","author":"Uppendahl","year":"2023","journal-title":"J Child. Psychol. Psychiatry."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/bjc.12333","article-title":"Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis","volume":"61","author":"Shorey","year":"2022","journal-title":"Br. J. Clin. Psychol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30187","DOI":"10.1038\/srep30187","article-title":"Prolonged secretion of cortisol as a possible mechanism underlying stress and depressive behaviour","volume":"6","author":"Qin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jad.2019.09.024","article-title":"Prenatal and childhood adverse life events, inflammation and depressive symptoms across adolescence","volume":"260","author":"Flouri","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1017\/S0033291720003992","article-title":"Dynamic interplay between life events and course of psychotic disorders: 10-year longitudinal study following first admission","volume":"52","author":"Donaldson","year":"2022","journal-title":"Psychol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1017\/S0033291721001410","article-title":"Polygenic liability, stressful life events and risk for secondary-treated depression in early life: A nationwide register-based case-cohort study","volume":"53","author":"Musliner","year":"2023","journal-title":"Psychol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1159\/000522540","article-title":"Chronic Stress and Steatosis of Muscles, Bones, Liver, and Pancreas: A Review","volume":"96","author":"Stefanaki","year":"2023","journal-title":"Horm. Res. Paediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0304-4157(85)90011-5","article-title":"Cholesterol and the cell membrane","volume":"822","author":"Yeagle","year":"1985","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature04399","article-title":"Role of cholesterol and lipid organization in disease","volume":"438","author":"Maxfield","year":"2005","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0065-2423(04)39003-7","article-title":"Cholesterol and lipids in depression: Stress, hypothalamo-pituitary-adrenocortical axis, and inflammation\/immunity","volume":"39","author":"Huang","year":"2005","journal-title":"Adv. Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Staurenghi, E., Giannelli, S., Testa, G., Sottero, B., Leonarduzzi, G., and Gamba, P. (2021). Cholesterol Dysmetabolism in Alzheimer\u2019s Disease: A Starring Role for Astrocytes?. Antioxidants, 10.","DOI":"10.3390\/antiox10121890"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.31083\/j.jin.2020.01.1249","article-title":"Stress causes cognitive impairment by affecting cholesterol efflux and reuptake leading to abnormalities in lipid metabolism of rats","volume":"19","author":"Ye","year":"2020","journal-title":"J. Integr. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1194\/jlr.M002196","article-title":"Chronic social defeat stress disrupts regulation of lipid synthesis","volume":"51","author":"Chuang","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.bbi.2015.02.008","article-title":"Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation","volume":"46","author":"Feng","year":"2015","journal-title":"Brain. Behav. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.freeradbiomed.2015.06.036","article-title":"New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death","volume":"87","author":"Noguchi","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41398-020-00874-7","article-title":"Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study","volume":"10","author":"Cattaneo","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.2478\/enr-2020-0027","article-title":"Glucose deprivation affects the expression of genes encoding cAMP-activated protein kinase and related proteins in U87 glioma cells in ERN1 dependent manner","volume":"54","author":"Ratushna","year":"2020","journal-title":"Endocr. Regul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.febslet.2015.01.001","article-title":"RIP140 triggers foam-cell formation by repressing ABCA1\/G1 expression and cholesterol efflux via liver X receptor","volume":"589","author":"He","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major depressive disorder: Hypothesis, mechanism, prevention and treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","unstructured":"(2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1789\u20131858."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mp.2016.120","article-title":"HPA axis in major depression: Cortisol, clinical symptomatology and genetic variation predict cognition","volume":"22","author":"Keller","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E382","DOI":"10.1152\/ajpendo.00410.2023","article-title":"Chronic cortisol stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain","volume":"326","author":"Blanco","year":"2024","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/brv.13039","article-title":"The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour","volume":"99","author":"Kerr","year":"2024","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.pnpbp.2019.01.010","article-title":"LDL cholesterol relates to depression, its severity, and the prospective course","volume":"92","author":"Wagner","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jad.2023.10.064","article-title":"The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of depression among US adults: A cross-sectional NHANES study","volume":"344","author":"Qi","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1007\/s12035-020-02232-6","article-title":"Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets","volume":"58","author":"Dai","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jsbmb.2019.03.003","article-title":"Alterations in cholesterol metabolism as a risk factor for developing Alzheimer\u2019s disease: Potential novel targets for treatment","volume":"190","author":"Goikolea","year":"2019","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.5607\/en.2019.28.5.554","article-title":"Cholesterol Metabolism in the Brain and Its Association with Parkinson\u2019s Disease","volume":"28","author":"Jin","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.15252\/emmm.201505413","article-title":"Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington\u2019s disease mice","volume":"7","author":"Valenza","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Aguzzoli, H.B., Brandon, J.A., Page, M.L., Nations, K.A., Dikobe, K.I., White, B.J., Gordon, L.A., Fox, G.A., Wadsworth, M.E., and Doyle, P.H. (2024). Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq. Nat. Biotechnol.","DOI":"10.1038\/s41587-024-02245-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1093\/brain\/aww255","article-title":"Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression","volume":"139","author":"Cheng","year":"2016","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s13238-014-0131-3","article-title":"Cholesterol metabolism and homeostasis in the brain","volume":"6","author":"Zhang","year":"2015","journal-title":"Protein Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.bbalip.2017.03.009","article-title":"New insights into cellular cholesterol acquisition: Promoter analysis of human HMGCR and SQLE, two key control enzymes in cholesterol synthesis","volume":"1862","author":"Howe","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/hipo.20743","article-title":"Cholesterol Homeostasis Markers are Localized to Mouse Hippocampal Pyramidal and Granule Layers","volume":"20","author":"Valdez","year":"2010","journal-title":"Hippocampus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.bbalip.2012.09.007","article-title":"Cholesterol efflux is differentially regulated in neurons and astrocytes: Implications for brain cholesterol homeostasis","volume":"1831","author":"Chen","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1093\/brain\/awv166","article-title":"CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer\u2019s disease","volume":"138","author":"Djelti","year":"2015","journal-title":"Brain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrn3075","article-title":"Erratum: Linking lipids to Alzheimer\u2019s disease: Cholesterol and beyond","volume":"12","author":"Kim","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2478\/enr-2019-0024","article-title":"Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells","volume":"53","author":"Riabovol","year":"2019","journal-title":"Endocr. Regul."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e18494","DOI":"10.1111\/jcmm.18494","article-title":"The TF\/Nrf2\/GSTP1 pathway is involved in stress-induced hepatocellular injury through ferroptosis","volume":"28","author":"Tian","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9979291","DOI":"10.1155\/2023\/9979291","article-title":"Bioinformatics Analysis of Molecular Interactions between Endoplasmic Reticulum Stress and Ferroptosis under Stress Exposure","volume":"2023","author":"Zhu","year":"2023","journal-title":"Anal. Cell. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:22:41Z","timestamp":1760109761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,24]]},"references-count":50,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158075"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158075","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,24]]}}}