{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:04Z","timestamp":1787027704359,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Science Foundation, Fujian Province","award":["2020J01647"],"award-info":[{"award-number":["2020J01647"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Objectives: Patients with occlusal disharmony (OD) may be susceptible to depression. The hypothalamus\u2013pituitary\u2013adrenal axis, 5-HT and 5HT2AR in the prefrontal cortex (PFC), amygdala, and hippocampus are involved in the modulation of emotion and depression. This study investigated whether OD affects the HPA axis and 5-HT system and, subsequently, produces depression-like behaviors in rats. Materials and methods: OD was produced by removing 0.5 and 0.25 mm of hard tissue from the cusps of the maxillary molars in randomly selected sides of Sprague\u2013Dawley rats. CUS involved exposure to 2 different stressors per day for 35 days. OD-, CUS-, and OD + CUS-treated groups and an untreated control group were compared in terms of behavior, endocrine status and brain histology. Results: There were significant differences among the four groups in the behavior tests (p &lt; 0.05), especially in the sucrose preference test, where there was a significant decrease in the OD group compared to the control group. ACTH and CORT concentrations were significantly higher in the OD + CUS group than the control group (p &lt; 0.05). Expression of GR and 5-HT2AR in the PFC, amygdala and hippocampal CA1 was significantly higher in the OD, CUS and OD + CUS groups than the control group (p &lt; 0.05). Conclusion: OD promotes depression-like behaviors through peripheral and central pathways via the HPA axis, GR and 5-HT system.<\/jats:p>","DOI":"10.3390\/brainsci12060747","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Occlusal Disharmony\u2014A Potential Factor Promoting Depression in a Rat Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Sihui","family":"Zhang","sequence":"first","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"},{"name":"Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixun","family":"He","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Lin","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6879-6525","authenticated-orcid":false,"given":"Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"},{"name":"Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jad.2019.05.079","article-title":"Test of a clinical model of poor physical health and suicide: The role of depression, psychosocial stress, interpersonal conflict, and panic","volume":"257","author":"Black","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_2","first-page":"1","article-title":"Psychological Issues for Patients Undergoing Stem Cell Therapy and Regenerative Medicine","volume":"7","author":"Braunsteiner","year":"2018","journal-title":"Open J. Regen. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0896-6273(02)00653-0","article-title":"Neurobiology of depression","volume":"34","author":"Nestler","year":"2002","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1093\/clinchem\/34.5.807","article-title":"The changing epidemiology of depression","volume":"34","author":"Klerman","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.neulet.2014.10.031","article-title":"Chronic unpredictable stress impairs endogenous antioxidant defense in rat brain","volume":"584","author":"Che","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/0091-3057(82)90053-3","article-title":"Animal model of depression: Pharmacological sensitivity of a hedonic deficit","volume":"16","author":"Katz","year":"1982","journal-title":"Pharm. Biochem. Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.conb.2014.08.013","article-title":"Depression: From psychopathology to pathophysiology","volume":"30","author":"Belzung","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ynstr.2016.08.002","article-title":"The chronic mild stress (CUS) model of depression: History, evaluation and usage","volume":"6","author":"Willner","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref_9","first-page":"319","article-title":"Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation","volume":"134","author":"Willner","year":"1997","journal-title":"Psy-chopharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/00008877-200205000-00001","article-title":"The validity of animal models of predisposition to depression","volume":"13","author":"Willner","year":"2002","journal-title":"Behav. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ynstr.2016.08.001","article-title":"Reliability of the chronic mild stress model of depression: A user survey","volume":"6","author":"Willner","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"The Academy of prosthodontics (2017). The Glossary of Prosthodontic Terms: Ninth Edition. J. Prosthet. Dent., 117, e1\u2013e105.","DOI":"10.1016\/j.prosdent.2016.12.001"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"989","DOI":"10.14219\/jada.archive.2012.0325","article-title":"Pain and persistent occlusal awareness: What should dentists do?","volume":"143","author":"Morrow","year":"2012","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00784-018-2534-7","article-title":"Prefrontal modulation during chewing performance in occlusal dysesthesia patients: A functional near-infrared spectroscopy study","volume":"23","author":"Narita","year":"2019","journal-title":"Clin. Oral Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"142","DOI":"10.11607\/ijp.4833","article-title":"Occlusal Dysesthesia: A Clinical Report on the Psychosomatic Man-agement of a Japanese Patient Cohort","volume":"30","author":"Oguchi","year":"2017","journal-title":"Int. J. Prosthodont."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/j.1365-2842.2012.02300.x","article-title":"Occlusal dysesthesia: A qualitative systematic review of the epidemi-ology, aetiology and management","volume":"39","author":"Hara","year":"2012","journal-title":"J. Oral Rehabil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.pnpbp.2017.02.006","article-title":"Experimental occlusal disharmony\u2014A promoting factor for anxiety in rats under chronic psychological stress","volume":"75","author":"Tang","year":"2017","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12017-011-8151-0","article-title":"Occlusal disharmony increases amyloid-beta in the rat hippocampus","volume":"13","author":"Ekuni","year":"2011","journal-title":"NeuroMolecular Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fnmol.2019.00174","article-title":"Malocclusion Generates Anxiety-Like Behavior Through a Putative Lateral Habenula-Mesencephalic Trigeminal Nucleus Pathway","volume":"12","author":"Liu","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system","volume":"5","author":"Chrousos","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.psyneuen.2018.05.020","article-title":"Emerging literature in the Microbiota-Brain Axis and Perinatal Mood and Anxiety Disorders","volume":"95","author":"Rackers","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.steroids.2017.07.006","article-title":"Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice","volume":"125","author":"Zeni","year":"2017","journal-title":"Steroids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.euroneuro.2013.04.013","article-title":"Developments in the field of antidepressants, where do we go now?","volume":"25","author":"Artigas","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_24","first-page":"10","article-title":"Poverty and language development: Roles of parenting and stress","volume":"10","author":"Perkins","year":"2013","journal-title":"Innov. Clin. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Azuma, K., Zhou, Q., Niwa, M., and Kubo, K.Y. (2017). Association between Mastication, the Hippocampus, and the HPA Axis: A Compre-hensive Review. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081687"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.archoralbio.2016.03.020","article-title":"Novel stress increases hypothalamic-pituitary-adrenal activity in mice with a raised bite","volume":"68","author":"Miyake","year":"2016","journal-title":"Arch. Oral Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5.9.1","DOI":"10.1002\/0471141755.ph0509s57","article-title":"Models of Affective Illness: Chronic Mild Stress in the Rat","volume":"57","author":"Papp","year":"2012","journal-title":"Curr. Protoc. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/ejo\/cjq121","article-title":"Relationship between impacts attributed to malocclusion and psychological stress in young Japanese adults","volume":"33","author":"Ekuni","year":"2011","journal-title":"Eur. J. Orthod."},{"key":"ref_29","first-page":"1","article-title":"Occlusal dysfunction and stress. An experimental study in macaque monkeys","volume":"8","year":"2010","journal-title":"J. Oral Rehabil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1708-8208.2009.00252.x","article-title":"Tactile sensibility of single-tooth implants and natural teeth under local anesthesia of the natural antagonistic teeth","volume":"14","author":"Enkling","year":"2012","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuroscience.2013.12.065","article-title":"Soft-diet feeding after weaning affects behavior in mice: Potential increase in vulnerability to mental disorders","volume":"263","author":"Watahiki","year":"2014","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1055\/s-2007-1014338","article-title":"Effects of Moclobemide, a New Generation Reversible Mao-A Inhibitor, in a Novel Animal Model of Depression","volume":"26","author":"Moreau","year":"1993","journal-title":"Pharmacopsychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/cphy.c150015","article-title":"Regulation of the Hypothalam-ic-Pituitary-Adrenocortical Stress Response","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/sj.mp.4001032","article-title":"Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH\/NE states","volume":"7","author":"Gold","year":"2002","journal-title":"Mol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.yfrne.2003.07.001","article-title":"Central mechanisms of stress integration: Hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness","volume":"24","author":"Herman","year":"2003","journal-title":"Front. Neuroendocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/14728222.2019.1572747","article-title":"Neuronal and behavioral plasticity: The role of serotonin and BDNF systems tandem","volume":"23","author":"Popova","year":"2019","journal-title":"Expert Opin. Targets"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.pharmthera.2012.09.006","article-title":"Serotonin receptors involved in antidepressant effects","volume":"137","author":"Artigas","year":"2013","journal-title":"Pharm. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/syn.890150310","article-title":"Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nu-clei","volume":"15","author":"Bel","year":"1993","journal-title":"Synapse"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13041-017-0306-y","article-title":"The role of 5-HT receptors in depression","volume":"10","author":"Yohn","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0028-3908(99)00010-6","article-title":"A review of central 5-HT receptors and their function","volume":"38","author":"Barnes","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_41","first-page":"5103","article-title":"Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress","volume":"8","author":"Hongli","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.alcohol.2020.04.002","article-title":"On the interaction between BDNF and serotonin systems: The effects of long-term ethanol consumption in mice","volume":"87","author":"Popova","year":"2020","journal-title":"Alcohol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1523\/JNEUROSCI.1438-19.2020","article-title":"Astrocytes Modulate Baroreflex Sensitivity at the Level of the Nucleus of the Solitary Tract","volume":"40","author":"Mastitskaya","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbrc.2014.11.036","article-title":"QCM-4, a 5-HT(3) receptor antagonist ameliorates plasma HPA axis hyperactivity, leptin resistance and brain oxidative stress in depression and anxiety-like behavior in obese mice","volume":"456","author":"Kurhe","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0165-6147(94)90315-8","article-title":"Current advances and trends in the treatment of depression","volume":"15","author":"Blier","year":"1994","journal-title":"Trends Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/cns.12247","article-title":"Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders","volume":"20","author":"Naumenko","year":"2014","journal-title":"CNS Neurosci. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/eos.12093","article-title":"Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis","volume":"121","author":"Cavalcante","year":"2013","journal-title":"Eur. J. Oral Sci."},{"key":"ref_48","first-page":"2486","article-title":"Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking","volume":"125","author":"Renner","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_49","first-page":"624","article-title":"Occlusion and brain function: Mastication as a prevention of cognitive dysfunction","volume":"37","author":"Ono","year":"2010","journal-title":"J. Oral Rehabil."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3389\/fphar.2018.00604","article-title":"Vaccinium bracteatum Leaf Extract Reverses Chronic Restraint Stress-Induced Depression-Like Behavior in Mice: Regulation of Hypothalamic-Pituitary-Adrenal Axis, Serotonin Turnover Systems, and ERK\/Akt Phosphorylation","volume":"9","author":"Oh","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"104516","DOI":"10.1016\/j.archoralbio.2019.104516","article-title":"Adverse effects of the bite-raised condition in animal studies: A systematic review","volume":"107","author":"Piancino","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00213-004-1774-1","article-title":"Corticosteroid-serotonin interactions in depression: A review of the human evidence","volume":"173","author":"Porter","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1523\/JNEUROSCI.0004-08.2008","article-title":"Failure to mount adaptive responses to stress results in dysregulation and cell death in the midbrain raphe","volume":"28","author":"McEuen","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fendo.2016.00137","article-title":"Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation","volume":"7","author":"Herman","year":"2016","journal-title":"Front. Endocrinol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:25:29Z","timestamp":1760138729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["brainsci12060747"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12060747","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,7]]}}}