{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:35:41Z","timestamp":1788917741904,"version":"build-2803163510"},"reference-count":117,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["#421143\/2018-5"],"award-info":[{"award-number":["#421143\/2018-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["#312215\/2021-5"],"award-info":[{"award-number":["#312215\/2021-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["UVic-FAPESP SPRINT 1\/2018"],"award-info":[{"award-number":["UVic-FAPESP SPRINT 1\/2018"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#421143\/2018-5"],"award-info":[{"award-number":["#421143\/2018-5"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["#312215\/2021-5"],"award-info":[{"award-number":["#312215\/2021-5"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["UVic-FAPESP SPRINT 1\/2018"],"award-info":[{"award-number":["UVic-FAPESP SPRINT 1\/2018"]}]},{"name":"University of Victoria (UVic, Victoria, BC, Canada)\u2014S\u00e3o Paulo Research Foundation (FAPESP, S\u00e3o Paulo, SP, Brazil) SPRINT Partnership","award":["#421143\/2018-5"],"award-info":[{"award-number":["#421143\/2018-5"]}]},{"name":"University of Victoria (UVic, Victoria, BC, Canada)\u2014S\u00e3o Paulo Research Foundation (FAPESP, S\u00e3o Paulo, SP, Brazil) SPRINT Partnership","award":["#312215\/2021-5"],"award-info":[{"award-number":["#312215\/2021-5"]}]},{"name":"University of Victoria (UVic, Victoria, BC, Canada)\u2014S\u00e3o Paulo Research Foundation (FAPESP, S\u00e3o Paulo, SP, Brazil) SPRINT Partnership","award":["UVic-FAPESP SPRINT 1\/2018"],"award-info":[{"award-number":["UVic-FAPESP SPRINT 1\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium\u2013phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.<\/jats:p>","DOI":"10.3390\/ijms23137077","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety"],"prefix":"10.3390","volume":"23","author":[{"given":"Bruna R.","family":"Kouba","sequence":"first","affiliation":[{"name":"Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florian\u00f3polis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-4865","authenticated-orcid":false,"given":"Anderson","family":"Camargo","sequence":"additional","affiliation":[{"name":"Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florian\u00f3polis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4982-1662","authenticated-orcid":false,"given":"Joana","family":"Gil-Mohapel","sequence":"additional","affiliation":[{"name":"Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada"},{"name":"Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-8780","authenticated-orcid":false,"given":"Ana L\u00facia S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florian\u00f3polis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17024","DOI":"10.1038\/nrdp.2017.24","article-title":"Anxiety Disorders","volume":"3","author":"Craske","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major Depressive Disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4088\/JCP.10m06176blu","article-title":"Comorbidity Patterns of Anxiety and Depressive Disorders in a Large Cohort Study: The Netherlands Study of Depression and Anxiety (NESDA)","volume":"72","author":"Lamers","year":"2011","journal-title":"J. Clin. Psychiatry"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"e12423","DOI":"10.1111\/gbb.12423","article-title":"Epigenetics at the Crossroads between Genes, Environment and Resilience in Anxiety Disorders: Epigenetics in Anxiety Disorders","volume":"17","author":"Schiele","year":"2018","journal-title":"Genes Brain Behav."},{"key":"ref_6","first-page":"46","article-title":"Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for Innovative Therapy","volume":"8","author":"Klein","year":"2017","journal-title":"Front. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/ejn.14631","article-title":"Gut Microbiota-Brain Axis in Depression: The Role of Neuroinflammation","volume":"53","author":"Carlessi","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2174\/1570159X15666170913110426","article-title":"Neuroinflammation and the Immune-Kynurenine Pathway in Anxiety Disorders","volume":"16","author":"Kim","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1136\/gutjnl-2017-314759","article-title":"Increased Human Intestinal Barrier Permeability Plasma Biomarkers Zonulin and FABP2 Correlated with Plasma LPS and Altered Gut Microbiome in Anxiety or Depression","volume":"67","author":"Stevens","year":"2018","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1515\/folmed-2017-0022","article-title":"Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced Anxiety-Like Behavior of Adult Female Rats","volume":"59","author":"Fedotova","year":"2017","journal-title":"Folia Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/1028415X.2019.1665854","article-title":"Protective Effects of Vitamin D on Neurophysiologic Alterations in Brain Aging: Role of Brain-Derived Neurotrophic Factor (BDNF)","volume":"24","author":"Khairy","year":"2021","journal-title":"Nutr. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/jnr.10491","article-title":"Vitamin D3 Inhibits Proinflammatory Cytokines and Nitric Oxide Production by the EOC13 Microglial Cell Line","volume":"71","author":"Bernard","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1007\/s12035-017-0839-1","article-title":"Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer\u2019s Disease","volume":"55","author":"Morello","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41423-019-0223-3","article-title":"The Benefits of Neuroinflammation for the Repair of the Injured Central Nervous System","volume":"16","author":"Yong","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrd.2016.39","article-title":"Resolution of Inflammation: A New Therapeutic Frontier","volume":"15","author":"Fullerton","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1172\/JCI34431","article-title":"A Calculated Response: Control of Inflammation by the Innate Immune System","volume":"118","author":"Barton","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbi.2018.06.010","article-title":"Principles of Inflammasome Priming and Inhibition: Implications for Psychiatric Disorders","volume":"73","author":"Herman","year":"2018","journal-title":"Brain. Behav. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 Polarization and Metabolic States: Microglia Bioenergetics with Acute Polarization","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1007\/s12035-020-01961-y","article-title":"The Microbiota-Gut-Immune-Glia (MGIG) Axis in Major Depression","volume":"57","author":"Rudzki","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.3389\/fimmu.2018.02305","article-title":"Regulation of NLRP3 Inflammasome by Phosphorylation","volume":"9","author":"Song","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1089\/ars.2015.6615","article-title":"Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming","volume":"26","author":"Liu","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00011-017-1095-6","article-title":"Nrf2\/ARE Pathway Inhibits ROS-Induced NLRP3 Inflammasome Activation in BV2 Cells after Cerebral Ischemia Reperfusion","volume":"67","author":"Xu","year":"2018","journal-title":"Inflamm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/nyas.12458","article-title":"Mechanism of NLRP3 Inflammasome Activation","volume":"1319","author":"Sutterwala","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tejeda, G., and D\u00edaz-Guerra, M. (2017). Integral Characterization of Defective BDNF\/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020268"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.it.2007.01.005","article-title":"Astrocytes Are Active Players in Cerebral Innate Immunity","volume":"28","author":"Farina","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/ejn.14720","article-title":"Neuroinflammation and Depression: A Review","volume":"53","author":"Troubat","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fphar.2019.00452","article-title":"Quinolinic Acid and Nuclear Factor Erythroid 2-Related Factor 2 in Depression: Role in Neuroprogression","volume":"10","author":"Bansal","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4137\/IJTR.S2318","article-title":"Effects of Kynurenine Pathway Metabolites on Intracellular NAD + Synthesis and Cell Death in Human Primary Astrocytes and Neurons","volume":"2","author":"Braidy","year":"2009","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1016\/j.bbamcr.2016.09.014","article-title":"Quinolinic Acid Neurotoxicity: Differential Roles of Astrocytes and Microglia via FGF-2-Mediated Signaling in Redox-Linked Cytoskeletal Changes","volume":"1863","author":"Pierozan","year":"2016","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-021-02175-2","article-title":"Tryptophan-Kynurenine Metabolism: A Link between the Gut and Brain for Depression in Inflammatory Bowel Disease","volume":"18","author":"Chen","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1016\/j.celrep.2020.02.099","article-title":"Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine","volume":"30","author":"Siopi","year":"2020","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.31887\/DCNS.2009.11.3\/rsduman","article-title":"Neuronal Damage and Protection in the Pathophysiology and Treatment of Psychiatric Illness: Stress and Depression","volume":"11","author":"Duman","year":"2009","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jcot.2019.07.004","article-title":"Vitamin D for Skeletal and Non-Skeletal Health: What We Should Know","volume":"10","author":"Charoenngam","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"872","DOI":"10.2310\/JIM.0b013e318214ea2d","article-title":"Vitamin D: A D-Lightful Solution for Health","volume":"59","author":"Holick","year":"2011","journal-title":"J. Investig. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D Deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.abb.2012.01.013","article-title":"Vitamin D 25-Hydroxylase\u2014Four Decades of Searching, Are We There Yet?","volume":"523","author":"Zhu","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.mayocp.2013.05.011","article-title":"Vitamin D for Health: A Global Perspective","volume":"88","author":"Holick","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3390\/nu5010111","article-title":"Vitamin D\u2014Effects on Skeletal and Extraskeletal Health and the Need for Supplementation","volume":"5","author":"Wacker","year":"2013","journal-title":"Nutrients"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00223-012-9619-0","article-title":"Molecular Mechanisms of Vitamin D Action","volume":"92","author":"Haussler","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.3390\/nu5093605","article-title":"Vitamin D: Deficiency, Sufficiency and Toxicity","volume":"5","author":"Alshahrani","year":"2013","journal-title":"Nutrients"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jchemneu.2004.08.006","article-title":"Distribution of the Vitamin D Receptor and 1\u03b1-Hydroxylase in Human Brain","volume":"29","author":"Eyles","year":"2005","journal-title":"J. Chem. Neuroanat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s40263-019-00640-4","article-title":"Potential Role of Vitamin D for the Management of Depression and Anxiety","volume":"33","author":"Casseb","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1001\/archpsyc.65.5.508","article-title":"Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults","volume":"65","author":"Hoogendijk","year":"2008","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10067-017-3874-4","article-title":"Prevalence of Depression and Anxiety in Rheumatoid Arthritis Patients and Their Associations with Serum Vitamin D Level","volume":"37","author":"Pu","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.coph.2010.04.001","article-title":"Vitamin D: Modulator of the Immune System","volume":"10","author":"Baeke","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102203","DOI":"10.1016\/j.redox.2021.102203","article-title":"1,25-Dihydroxyvitamin D3 Attenuates IL-1\u03b2 Secretion by Suppressing NLRP1 Inflammasome Activation by Upregulating the NRF2-HO-1 Pathway in Epidermal Keratinocytes","volume":"48","author":"Nakajo","year":"2021","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10787-017-0372-x","article-title":"Vitamin D3 Attenuates Cognitive Deficits and Neuroinflammatory Responses in ICV-STZ Induced Sporadic Alzheimer\u2019s Disease","volume":"26","author":"Yamini","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101295","DOI":"10.1016\/j.redox.2019.101295","article-title":"Vitamin D Receptor Activation Regulates Microglia Polarization and Oxidative Stress in Spontaneously Hypertensive Rats and Angiotensin II-Exposed Microglial Cells: Role of Renin-Angiotensin System","volume":"26","author":"Cui","year":"2019","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jneuroim.2016.01.015","article-title":"Vitamin D3 Alters Microglia Immune Activation by an IL-10 Dependent SOCS3 Mechanism","volume":"292","author":"Boontanrart","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11481-016-9720-7","article-title":"Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson\u2019s Disease, Shifting M1 to M2 Microglia Responses","volume":"12","author":"Calvello","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2013.12.012","article-title":"1,25-Dihydroxyvitamin D3 up-Regulates TLR10 While down-Regulating TLR2, 4, and 5 in Human Monocyte THP-1","volume":"141","author":"Verma","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000444300","article-title":"1,25-Dihydroxyvitamin D3 Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells","volume":"23","author":"Verma","year":"2016","journal-title":"Neuroimmunomodulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"172971","DOI":"10.1016\/j.pbb.2020.172971","article-title":"Cholecalciferol Abolishes Depressive-like Behavior and Hippocampal Glucocorticoid Receptor Impairment Induced by Chronic Corticosterone Administration in Mice","volume":"196","author":"Camargo","year":"2020","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s10753-018-0928-y","article-title":"1,25-Dihydroxy Vitamin D3 Attenuates the Oxidative Stress-Mediated Inflammation Induced by PM2.5via the P38\/NF-\u039aB\/NLRP3 Pathway","volume":"42","author":"Xin","year":"2019","journal-title":"Inflammation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105789","DOI":"10.1016\/j.jsbmb.2020.105789","article-title":"Vitamin D\/VDR Attenuate Cisplatin-Induced AKI by down-Regulating NLRP3\/Caspase-1\/GSDMD Pyroptosis Pathway","volume":"206","author":"Jiang","year":"2021","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1093\/ndt\/gfi254","article-title":"Vitamin D Decreases NF\u03baB Activity by Increasing I\u03baB\u03b1 Levels","volume":"21","author":"Shany","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/cei.13164","article-title":"Vitamin D Receptor Interacts with NLRP3 to Restrict the Allergic Response","volume":"194","author":"Huang","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.3389\/fimmu.2019.02783","article-title":"Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination","volume":"10","author":"Rao","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s10020-021-00377-1","article-title":"Calcitriol Confers Neuroprotective Effects in Traumatic Brain Injury by Activating Nrf2 Signaling through an Autophagy-Mediated Mechanism","volume":"27","author":"Cui","year":"2021","journal-title":"Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"100942","DOI":"10.1016\/j.arr.2019.100942","article-title":"Shaping the Nrf2-ARE-Related Pathways in Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"54","author":"Mota","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"104893","DOI":"10.1016\/j.neuint.2020.104893","article-title":"Vitamin D Exerts Neuroprotection via SIRT1\/Nrf-2\/NF-KB Signaling Pathways against D-Galactose-Induced Memory Impairment in Adult Mice","volume":"142","author":"Ali","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1080\/01616412.2020.1787624","article-title":"Administration of Vitamin D3 and E Supplements Reduces Neuronal Loss and Oxidative Stress in a Model of Rats with Alzheimer\u2019s Disease","volume":"42","author":"Mehrabadi","year":"2020","journal-title":"Neurol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/1097-4547(20001101)62:3<374::AID-JNR7>3.0.CO;2-7","article-title":"Effect of 1,25-Dihydroxyvitamin D3 on Cultured Mesencephalic Dopaminergic Neurons to the Combined Toxicity Caused by L-Buthionine Sulfoximine and 1-Methyl-4-Phenylpyridine","volume":"62","author":"Shinpo","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ijdevneu.2007.03.006","article-title":"Maternal Vitamin D Depletion Alters Neurogenesis in the Developing Rat Brain","volume":"25","author":"Cui","year":"2007","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/hipo.20908","article-title":"Abnormal Neurogenesis in the Dentate Gyrus of Adult Mice Lacking 1,25-Dihydroxy Vitamin D3 (1,25-(OH)2D3)","volume":"22","author":"Zhu","year":"2012","journal-title":"Hippocampus"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jsbmb.2006.12.096","article-title":"Developmental Vitamin D Deficiency Alters the Expression of Genes Encoding Mitochondrial, Cytoskeletal and Synaptic Proteins in the Adult Rat Brain","volume":"103","author":"Eyles","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/pmic.200600392","article-title":"Developmental Vitamin D Deficiency Alters Brain Protein Expression in the Adult Rat: Implications for Neuropsychiatric Disorders","volume":"7","author":"Almeras","year":"2007","journal-title":"PROTEOMICS"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0306-4522(03)00040-X","article-title":"Vitamin D3 and Brain Development","volume":"118","author":"Eyles","year":"2003","journal-title":"Neuroscience"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.brainresbull.2004.12.007","article-title":"Developmental Vitamin D3 Deficiency Alters the Adult Rat Brain","volume":"65","author":"Burne","year":"2005","journal-title":"Brain Res. Bull."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1097\/00001756-199609020-00023","article-title":"1,25-Dihydroxyvitamin D3, an Inducer of Glial Cell Line-Derived Neurotrophic Factor","volume":"7","author":"Naveilhan","year":"1996","journal-title":"NeuroReport"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.neures.2020.08.002","article-title":"Vitamin D3\/Vitamin D Receptor Signaling Mitigates Symptoms of Post-Stroke Depression in Mice by Upregulating Hippocampal BDNF Expression","volume":"170","author":"Xu","year":"2021","journal-title":"Neurosci. Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Koshkina, A., Dudnichenko, T., Baranenko, D., Fedotova, J., and Drago, F. (2019). Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications. Nutrients, 11.","DOI":"10.3390\/nu11081726"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/00001756-199412300-00032","article-title":"1,25-Dihydroxyvitamin D3 Regulates NT-3, NT-4 but Not BDNF MRNA in Astrocytes","volume":"6","author":"Neveu","year":"1994","journal-title":"NeuroReport"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mcn.2018.03.013","article-title":"Mechanisms of Neurotrophin Trafficking via Trk Receptors","volume":"91","author":"Kuruvilla","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.neuropharm.2012.10.004","article-title":"Combination Treatment with Progesterone and Vitamin D Hormone Is More Effective than Monotherapy in Ischemic Stroke: The Role of BDNF\/TrkB\/Erk1\/2 Signaling in Neuroprotection","volume":"67","author":"Atif","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev-med-053013-062946","article-title":"Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics","volume":"66","author":"Abdallah","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1190287","article-title":"MTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/73888","article-title":"Synapsins as Mediators of BDNF-Enhanced Neurotransmitter Release","volume":"3","author":"Jovanovic","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s12031-019-01461-2","article-title":"Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder","volume":"70","author":"Alghamdi","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2174\/1871527318666190703103709","article-title":"The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"18","author":"Seyedi","year":"2019","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6048","DOI":"10.3390\/nu6126048","article-title":"Neurochemical Effects of Chronic Administration of Calcitriol in Rats","volume":"6","author":"Jiang","year":"2014","journal-title":"Nutrients"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neuroscience.2016.07.020","article-title":"Vitamin D Signaling and the Differentiation of Developing Dopamine Systems","volume":"333","author":"Pertile","year":"2016","journal-title":"Neuroscience"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12263-018-0605-7","article-title":"Optimal Vitamin D Spurs Serotonin: 1,25-Dihydroxyvitamin D Represses Serotonin Reuptake Transport (SERT) and Degradation (MAO-A) Gene Expression in Cultured Rat Serotonergic Neuronal Cell Lines","volume":"13","author":"Sabir","year":"2018","journal-title":"Genes Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.metabol.2017.01.007","article-title":"Gut Microbiota Interactions with the Immunomodulatory Role of Vitamin D in Normal Individuals","volume":"69","author":"Luthold","year":"2017","journal-title":"Metabolism"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1093\/infdis\/jiu235","article-title":"Vitamin D Deficiency Promotes Epithelial Barrier Dysfunction and Intestinal Inflammation","volume":"210","author":"Assa","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3945\/jn.113.180794","article-title":"Vitamin D Regulates the Gut Microbiome and Protects Mice from Dextran Sodium Sulfate\u2013Induced Colitis","volume":"143","author":"Ooi","year":"2013","journal-title":"J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"686","DOI":"10.2353\/ajpath.2010.090998","article-title":"Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-\u039aB Activity in Intestine","volume":"177","author":"Wu","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.biopha.2016.10.107","article-title":"Different Effects of Vitamin D Hormone Treatment on Depression-like Behavior in the Adult Ovariectomized Female Rats","volume":"84","author":"Fedotova","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fedotova, J.O. (2019). Vitamin D3 Treatment Differentially Affects Anxiety-like Behavior in the Old Ovariectomized Female Rats and Old Ovariectomized Female Rats Treated with Low Dose of 17\u03b2-Estradiol. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0774-2"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ejphar.2018.07.002","article-title":"Cholecalciferol Counteracts Depressive-like Behavior and Oxidative Stress Induced by Repeated Corticosterone Treatment in Mice","volume":"833","author":"Camargo","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00210-019-01714-2","article-title":"Effects of Cholecalciferol on Behavior and Production of Reactive Oxygen Species in Female Mice Subjected to Corticosterone-Induced Model of Depression","volume":"393","author":"Neis","year":"2020","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1007\/s11011-022-00979-6","article-title":"Involvement of Serotonergic Neurotransmission in the Antidepressant-like Effect Elicited by Cholecalciferol in the Chronic Unpredictable Stress Model in Mice","volume":"37","author":"Neis","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"106734","DOI":"10.1016\/j.intimp.2020.106734","article-title":"Neuroprotective Effects of Vitamin D and 17\u00df-Estradiol against Ovariectomy-Induced Neuroinflammation and Depressive-like State: Role of the AMPK\/NF-\u039aB Pathway","volume":"86","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00210-020-02002-0","article-title":"Beneficial Effects of Vitamin D on Anxiety and Depression-like Behaviors Induced by Unpredictable Chronic Mild Stress by Suppression of Brain Oxidative Stress and Neuroinflammation in Rats","volume":"394","author":"Izadi","year":"2021","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1016\/j.psyneuen.2013.03.017","article-title":"Stress and Vitamin D: Altered Vitamin D Metabolism in Both the Hippocampus and Myocardium of Chronic Unpredictable Mild Stress Exposed Rats","volume":"38","author":"Jiang","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Groves, N.J., Bradford, D., Sullivan, R.K.P., Conn, K.A., Aljelaify, R.F., McGrath, J.J., and Burne, T.H.J. (2016). Behavioural Effects of Adult Vitamin D Deficiency in BALB\/c Mice Are Not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152328"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-2796.2008.02008.x","article-title":"Effects of Vitamin D Supplementation on Symptoms of Depression in Overweight and Obese Subjects: Randomized Double-Blind Trial","volume":"264","author":"Jorde","year":"2008","journal-title":"J. Intern. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s10620-016-4396-7","article-title":"Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn\u2019s Disease in Remission: A Pilot Randomized Double-Blind Controlled Study","volume":"62","author":"Narula","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"8232863","DOI":"10.1155\/2017\/8232863","article-title":"Vitamin D Supplementation Improves Mood in Women with Type 2 Diabetes","volume":"2017","author":"Penckofer","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/19390211.2018.1472168","article-title":"Vitamin D Decreases Beck Depression Inventory Score in Patients with Mild to Moderate Ulcerative Colitis: A Double-Blind Randomized Placebo-Controlled Trial","volume":"16","author":"Sharifi","year":"2019","journal-title":"J. Diet. Suppl."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"110601","DOI":"10.1016\/j.nut.2019.110601","article-title":"Effects of Zinc, Vitamin D, and Their Co-Supplementation on Mood, Serum Cortisol, and Brain-Derived Neurotrophic Factor in Patients with Obesity and Mild to Moderate Depressive Symptoms: A Phase II, 12-Wk, 2 \u00d7 2 Factorial Design, Double-Blind, Randomized, Placebo-Controlled Trial","volume":"71","author":"Yosaee","year":"2020","journal-title":"Nutrition"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e01760","DOI":"10.1002\/brb3.1760","article-title":"Vitamin D Supplementation Improves Anxiety but Not Depression Symptoms in Patients with Vitamin D Deficiency","volume":"10","author":"Zhu","year":"2020","journal-title":"Brain Behav."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Hansen, J.P., Pareek, M., Hvolby, A., Schmedes, A., Toft, T., Dahl, E., and Nielsen, C.T. (2019). Vitamin D3 Supplementation and Treatment Outcomes in Patients with Depression (D3-Vit-Dep). BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4218-z"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jad.2020.03.029","article-title":"Effects of Vitamin D Supplementation on Depression and Some Involved Neurotransmitters","volume":"269","author":"Kaviani","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.clnu.2018.09.011","article-title":"Effect of Vitamin D Supplementation on Depression in Elderly Patients: A Randomized Clinical Trial","volume":"38","author":"Alavi","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/aje\/kwr482","article-title":"Vitamin D Supplementation and Depression in the Women\u2019s Health Initiative Calcium and Vitamin D Trial","volume":"176","author":"Powers","year":"2012","journal-title":"Am. J. Epidemiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/JCP.0b013e31828f619a","article-title":"The Effect of 2 Different Single Injections of High Dose of Vitamin D on Improving the Depression in Depressed Patients With Vitamin D Deficiency: A Randomized Clinical Trial","volume":"33","author":"Nabizade","year":"2013","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jpsychires.2020.07.037","article-title":"Effect of Adjunctive Single Dose Parenteral Vitamin D Supplementation in Major Depressive Disorder with Concurrent Vitamin D Deficiency: A Double-Blind Randomized Placebo-Controlled Trial","volume":"129","author":"Vellekkatt","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/0004867412465022","article-title":"Therapeutic Effects of Vitamin D as Adjunctive Therapy to Fluoxetine in Patients with Major Depressive Disorder","volume":"47","author":"Khoraminya","year":"2013","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1007\/s11011-019-00486-1","article-title":"Vitamin D Supplementation Ameliorates Severity of Generalized Anxiety Disorder (GAD)","volume":"34","author":"Eid","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2006.02.016","article-title":"Vitamin D receptor polymorphisms and diseases","volume":"371","author":"Valdivielso","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s12031-020-01719-0","article-title":"BsmI-ApaI-TaqI TAC (BAt) Haplotype of Vitamin D Receptor Gene Is Associated with Increased Risk of Major Depressive Disorder","volume":"71","author":"Lye","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Usategui-Mart\u00edn, R., De Luis-Rom\u00e1n, D.A., Fern\u00e1ndez-G\u00f3mez, J.M., Ruiz-Mambrilla, M., and P\u00e9rez-Castrill\u00f3n, J.L. (2022). Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients, 14.","DOI":"10.3390\/nu14020360"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:40:09Z","timestamp":1760139609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,25]]},"references-count":117,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137077"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137077","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,25]]}}}