Skip to content
2000
Volume 25, Issue 3
  • ISSN: 1871-5249
  • E-ISSN: 1875-6166

Abstract

Background

Major depressive disorder represents a complicated mental disorder characterized by persistent feelings of unhappiness and loss of interest. More evidence suggests a high potential correlation between vitamin D deficiency and depression. However, the underlying mechanisms and the therapeutic potential of vitamin D supplementation are still not properly understood. The purpose of this research is to evaluate the effect of vitamin D supplementation on depressive behaviors using a rat model of depression and explore the potential mechanisms involved.

Depression is a prevalent mental health disorder that significantly impacts the quality of life of individuals. Despite the availability of various treatment options, many patients still experience suboptimal outcomes, highlighting the need for further exploration of novel therapeutic approaches. In recent years, the importance of vitamin D in mental health, particularly in depression, has gained considerable attention.

Methods

In this project, we propose to utilize an animal model of depressed rats to evaluate the effect of vitamin D supplementation on depressive behaviors. We employed a range of well-established behavioral tests to assess changes in depressive-like behaviors following vitamin D supplementation.

Additionally, histopathological examinations of the hippocampal region, known to be involved in mood regulation, were performed to assess structural alterations and cellular changes associated with depression and vitamin D supplementation.

Results

The findings demonstrate the therapeutic potential of vitamin D supplementation by improving neuronal reorganization and proliferation in the hippocampus, suggesting an interest in investigating other mechanisms of interaction.

Conclusion

The findings of this research will provide valuable insight into the therapeutic potential of vitamin D in depression and shed light on the underlying mechanisms involved.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnsamc/10.2174/0118715249308068240903062701
2024-09-19
2025-11-04

  • From This Site

    /content/journals/cnsamc/10.2174/0118715249308068240903062701
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Dietary Reference Intakes for Calcium and Vitamin D.Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin DWashington (DC): National Academies Press (US)2011Available from: https://www.ncbi.nlm.nih.gov/books/NBK56061/
    [Google Scholar]
  2. GanmaaD. BromageS. KhudyakovP. ErdenenbaatarS. DelgererekhB. MartineauA.R. Influence of Vitamin D supplementation on growth, body composition, and pubertal development among school-aged children in an area with a high prevalence of Vitamin D deficiency.JAMA Pediatr.20231771324110.1001/jamapediatrics.2022.458136441522
     [Google Scholar]
  3. Vitamin D Receptor.2005Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/vitamin-d-receptor
  4. BouillonR. ManousakiD. RosenC. TrajanoskaK. RivadeneiraF. RichardsJ.B. The health effects of vitamin D supplementation: evidence from human studies.Nat. Rev. Endocrinol.20221829611010.1038/s41574‑021‑00593‑z34815552
     [Google Scholar]
  5. JacobsB. Adult brain neurogenesis and depression.Brain Behav. Immun.200216560260910.1016/S0889‑1591(02)00015‑612401475
     [Google Scholar]
  6. HanssonM. ChotaiJ. BodlundO. Patients’ beliefs about the cause of their depression.J. Affect. Disord.20101241-2545910.1016/j.jad.2009.10.03219923007
     [Google Scholar]
  7. WillnerP. The chronic mild stress (CMS) model of depression: History, evaluation and usage.Neurobiol. Stress20176789310.1016/j.ynstr.2016.08.00228229111
     [Google Scholar]
  8. ShelineY.I. Depression and the hippocampus: cause or effect?Biol. Psychiatry201170430830910.1016/j.biopsych.2011.06.00621791257
     [Google Scholar]
  9. KimE.J. PellmanB. KimJ.J. Stress effects on the hippocampus: a critical review.Learn. Mem.201522941141610.1101/lm.037291.11426286651
     [Google Scholar]
  10. Medina-RodriguezE.M. BeurelE. Blood brain barrier and inflammation in depression.Neurobiol. Dis.202217510592610.1016/j.nbd.2022.10592636375722
     [Google Scholar]
  11. LiuB. LiuJ. WangM. ZhangY. LiL. From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder.Front. Cell. Neurosci.20171130510.3389/fncel.2017.0030529033793
     [Google Scholar]
  12. SchumacherA. VillaruelF.R. UsslingA. RiazS. LeeA.C.H. ItoR. Ventral Hippocampal CA1 and CA3 Differentially Mediate Learned Approach-Avoidance Conflict Processing.Curr. Biol.201828813181324.e410.1016/j.cub.2018.03.01229606418
     [Google Scholar]
  13. MaharI. BambicoF.R. MechawarN. NobregaJ.N. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects.Neurosci. Biobehav. Rev.20143817319210.1016/j.neubiorev.2013.11.00924300695
     [Google Scholar]
  14. PriceJ.B. BronarsC. ErhardtS. CullenK.R. SchwielerL. BerkM. WalderK. McGeeS.L. FryeM.A. TyeS.J. Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression.Neurosci. Biobehav. Rev.20189021222010.1016/j.neubiorev.2018.04.00229656032
     [Google Scholar]
  15. HuangY.N. HoY.J. LaiC.C. ChiuC.T. WangJ.Y. 1,25-Dihydroxyvitamin D3 attenuates endotoxin-induced production of inflammatory mediators by inhibiting MAPK activation in primary cortical neuron-glia cultures.J. Neuroinflammation201512114710.1186/s12974‑015‑0370‑026259787
     [Google Scholar]
  16. NanriA. MizoueT. MatsushitaY. Poudel-TandukarK. SatoM. OhtaM. MishimaN. Association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese: analysis by survey season.Eur. J. Clin. Nutr.200963121444144710.1038/ejcn.2009.9619690578
     [Google Scholar]
  17. Dana-AlamdariL. KheirouriS. NoorazarS.G. Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder.Iran. J. Public Health201544569069726284211
     [Google Scholar]
  18. AnjumI. JafferyS.S. FayyazM. SamooZ. AnjumS. The Role of Vitamin D in Brain Health: A Mini Literature Review.Cureus2018107e296010.7759/cureus.296030214848
     [Google Scholar]
  19. RebelosE. TentolourisN. JudeE. The Role of Vitamin D in Health and Disease: A Narrative Review on the Mechanisms Linking Vitamin D with Disease and the Effects of Supplementation.Drugs202383866568510.1007/s40265‑023‑01875‑837148471
     [Google Scholar]
  20. Abdel-SalamO. BaiuomyA.R. ArbidM.S. Studies on the anti-inflammatory effect of fluoxetine in the rat.Pharmacol. Res.200449211913110.1016/j.phrs.2003.07.01614643692
     [Google Scholar]
  21. SauvéB. ChorfiY. MontminyM.P.L. GuayF. VitaminD. Vitamin D Supplementation Impacts Calcium and Phosphorus Metabolism in Piglets Fed a Diet Contaminated with Deoxynivalenol and Challenged with Lipopolysaccharides.Toxins (Basel)202315639410.3390/toxins1506039437368695
     [Google Scholar]
  22. PorsoltR.D. AntonG. BlavetN. JalfreM. Behavioural despair in rats: A new model sensitive to antidepressant treatments.Eur. J. Pharmacol.197847437939110.1016/0014‑2999(78)90118‑8204499
     [Google Scholar]
  23. Brenes SáenzJ.C. VillagraO.R. Fornaguera TríasJ. Factor analysis of Forced Swimming test, Sucrose Preference test and Open Field test on enriched, social and isolated reared rats.Behav. Brain Res.20061691576510.1016/j.bbr.2005.12.00116414129
     [Google Scholar]
  24. KadilY. FilaliH. Nigella Fixed Oil mitigates memory impairment in a rat aged model of cognitive decline, a pivotal role of BDNF and CREB signaling pathways in the hippocampus.CNS Neurol. Disord. Drug Targets20223035638539
     [Google Scholar]
  25. ChristakosS. DhawanP. VerstuyfA. VerlindenL. CarmelietG. VitaminD. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.Physiol. Rev.201696136540810.1152/physrev.00014.201526681795
     [Google Scholar]
  26. MilaneschiY. HoogendijkW. LipsP. HeijboerA.C. SchoeversR. van HemertA.M. BeekmanA.T.F. SmitJ.H. PenninxB.W.J.H. The association between low vitamin D and depressive disorders.Mol. Psychiatry201419444445110.1038/mp.2013.3623568194
     [Google Scholar]
  27. MikolaT. MarxW. LaneM.M. HockeyM. LoughmanA. RajapolviS. RocksT. O’NeilA. MischoulonD. Valkonen-KorhonenM. LehtoS.M. RuusunenA. The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials.Crit. Rev. Food Sci. Nutr.20236333117841180110.1080/10408398.2022.209656035816192
     [Google Scholar]
  28. CassebG.A.S. KasterM.P. RodriguesA.L.S. Potential Role of Vitamin D for the Management of Depression and Anxiety.CNS Drugs201933761963710.1007/s40263‑019‑00640‑431093951
     [Google Scholar]
  29. BerridgeM.J. Vitamin D and Depression: Cellular and Regulatory Mechanisms.Pharmacol. Rev.2017692809210.1124/pr.116.01322728202503
     [Google Scholar]
  30. FedotovaJ. DudnichenkoT. KruzliakP. PuchavskayaZ. Different effects of vitamin D hormone treatment on depression-like behavior in the adult ovariectomized female rats.Biomed. Pharmacother.2016841865187210.1016/j.biopha.2016.10.10727847201
     [Google Scholar]
  31. Bakhtiari-DovvombaygiH. IzadiS. ZareM. Asgari HassanloueiE. DinpanahH. Ahmadi-SoleimaniS.M. BeheshtiF. Vitamin D3 administration prevents memory deficit and alteration of biochemical parameters induced by unpredictable chronic mild stress in rats.Sci. Rep.20211111627110.1038/s41598‑021‑95850‑634381124
     [Google Scholar]
  32. Al-RamadhanF.R. AbulmeatyM.M.A. AlquraishiM. RazakS. AlhussainM.H. Effect of Vitamin D3 on Depressive Behaviors of Rats Exposed to Chronic Unpredictable Mild Stress.Biomedicines2023118211210.3390/biomedicines1108211237626608
     [Google Scholar]
  33. AygunH. AyyildizM. AgarE. Effects of vitamin D and paricalcitol on epileptogenesis and behavioral properties of WAG/Rij rats with absence epilepsy.Epilepsy Res.201915710620810.1016/j.eplepsyres.2019.10620831581040
     [Google Scholar]
  34. ZhangW. GuoY. WangK. ChenL. JiangP. Neuroprotective effects of vitamin D and 17ß-estradiol against ovariectomy-induced neuroinflammation and depressive-like state: Role of the AMPK/NF-κB pathway.Int. Immunopharmacol.20208610673410.1016/j.intimp.2020.10673432604067
     [Google Scholar]
  35. EylesD.W. VitaminD. Brain and Behavior.JBMR Plus202151e1041910.1002/jbm4.1041933553986
     [Google Scholar]
  36. CorreiaA.S. CardosoA. ValeN. BDNF Unveiled: Exploring Its Role in Major Depression Disorder Serotonergic Imbalance and Associated Stress Conditions.Pharmaceutics2023158208110.3390/pharmaceutics1508208137631295
     [Google Scholar]
  37. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression.Neural Regen Res.2015109142732
     [Google Scholar]
  38. KazemiF. BabriS. KeyhanmehrP. Farid-HabibiM. RadS.N. FarajdokhtF. Maternal vitamin D supplementation and treadmill exercise attenuated vitamin D deficiency-induced anxiety-and depressive-like behaviors in adult male offspring rats.Nutr. Neurosci.202326647048210.1080/1028415X.2022.205920335470763
     [Google Scholar]
  39. Bayo-OlugbamiA. NafiuA.B. AminA. OgundeleO.M. LeeC.C. OwoyeleB.V. Vitamin D attenuated 6-OHDA-induced behavioural deficits, dopamine dysmetabolism, oxidative stress, and neuro-inflammation in mice.Nutr. Neurosci.202225482383410.1080/1028415X.2020.181533132912107
     [Google Scholar]
/content/journals/cnsamc/10.2174/0118715249308068240903062701
Loading
Vitamin D Mitigates Depression-related Disorders in an Animal Model of Depression: A Behavioral, Anatomopahtological, and Molecular Investigation, Implicating the Hippocampal BDNF Signaling Pathway
Central Nervous System Agents in Medicinal Chemistry 25, 386 (2025); https://doi.org/10.2174/0118715249308068240903062701
/content/journals/cnsamc/10.2174/0118715249308068240903062701
/content/journals/cnsamc/10.2174/0118715249308068240903062701
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): BDNF; behavioral tests; Depression; histopathology; rat model; vitamin D

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test